Maria-Luisa Alegre

Research Summary
My laboratory is interested in T cell responses in settings of transplantation, autoimmunity and cancer, with an emphasis on mouse models and emerging extensions onto clinical translation. A main focus of the laboratory is on T cell tolerance in transplantation and how infections and inflammatory events can affect induction or maintenance of tolerance. We have found that transplantation tolerance can exist at different levels of robustness based on the number of mechanisms of T cell tolerance that are engaged, and that infections or inflammation can erode such tolerance. The impact of bacterial infections on transplant outcomes has led us to discover that the microbiota also influences immune responses to transplanted organs and can be manipulated to prolong graft survival. Our clinical studies have focused on the immunology of transplant recipients and of patients infected with the bacteria that influence transplant outcomes and, collaboratively, we have explored the involvement of the microbiota in the responsiveness of melanoma patients to immunotherapy.
Keywords
Immunology, Immunology, Transplantation, Transplant Rejection, Tolerance, Immune
Education
  • Universite Libre de Bruxelles, Brussels, Belgium, MD Medicine 06/1985
  • University of Chicago, Chicago, Illinois, PhD Immunology 08/1993
  • Universite Libre de Bruxelles, Brussels, Belgium, PhD Medical Sciences 06/1994
Biosciences Graduate Program Association
Awards & Honors
  • 1985 - MD Summa Cum Laude Universite Libre de Bruxelles
  • 1994 - Best PhD Dissertation The University of Chicago
  • 1994 - Intensive Care Competence Summa Cum Laude Universite Libre de Bruxelles
  • 2005 - Basic Science Career Development Award American Society of Transplantation
  • 2008 - Leif B. Sorenson Faculty Research Award The University of Chicago
  • 2011 - Basic Science Investigator Award American Society of Transplantation
  • 2018 - Paul S. Russell Visiting Professor Massachussetts General Hospital and Harvard Medical School
  • 2019 - Established Investigator Award American Society of Transplantation
Publications
  1. Sepulveda M, Pirozzolo I, Alegre ML. Impact of the microbiota on solid organ transplant rejection. Curr Opin Organ Transplant. 2019 Oct 01. View in: PubMed

  2. Alegre ML. Innate lymphoid cells coming of age. Am J Transplant. 2019 Oct; 19(10):2669. View in: PubMed

  3. Alegre ML. Fibroblasts can have subsets too! Am J Transplant. 2019 Sep; 19(9):2397. View in: PubMed

  4. McIntosh CM, Alegre ML. Teamwork by IL-10+ and IL-35+ Tregs. Am J Transplant. 2019 Aug; 19(8):2147. View in: PubMed

  5. Lei YM, Sepulveda M, Chen L, Wang Y, Pirozzolo I, Theriault B, Chong AS, Belkaid Y, Alegre ML. Skin-restricted commensal colonization accelerates skin graft rejection. JCI Insight. 2019 Jul 16; 5. View in: PubMed

  6. Alegre ML. Lymph node segregation for tolerance or inflammation. Am J Transplant. 2019 Jul; 19(7):1873. View in: PubMed

  7. Alegre ML. Mouse microbiomes: overlooked culprits of experimental variability. Genome Biol. 2019 05 29; 20(1):108. View in: PubMed

  8. Alegre ML. Neuroimmunology and the control of T cell migration. Am J Transplant. 2019 Jun; 19(6):1605. View in: PubMed

  9. Miller ML, Chong AS, Alegre ML. Fifty Shades of Tolerance: Beyond a Binary Tolerant/Non-Tolerant Paradigm. Curr Transplant Rep. 2017 Dec; 4(4):262-269. View in: PubMed

  10. Sepulveda M, Alegre ML. Harnessing the commensal microbiota to improve immune responses. Am J Transplant. 2019 May; 19(5):1257. View in: PubMed

  11. Alegre ML. Treg Respiration. Am J Transplant. 2019 Apr; 19(4):969. View in: PubMed

  12. Azzi J, Alegre ML. Outstanding questions in transplantation: An introduction to this minireview series. Am J Transplant. 2019 Aug; 19(8):2149-2150. View in: PubMed

  13. Alegre ML. A New Ligand for LAG-3. Am J Transplant. 2019 Mar; 19(3):617. View in: PubMed

  14. Rigat F, Bartolini E, Dalsass M, Kumar N, Marchi S, Speziale P, Maione D, Chen L, Romano MR, Alegre ML, Bagnoli F, Daum RS, David MZ. Retrospective Identification of a Broad IgG Repertoire Differentiating Patients With S. aureus Skin and Soft Tissue Infections From Controls. Front Immunol. 2019; 10:114. View in: PubMed

  15. Gupta PK, McIntosh CM, Chong AS, Alegre ML. The pursuit of transplantation tolerance: new mechanistic insights. Cell Mol Immunol. 2019 Apr; 16(4):324-333. View in: PubMed

  16. Alegre ML. A molecular pathway for indirect presentation? Am J Transplant. 2019 Feb; 19(2):311. View in: PubMed

  17. Rael VE, Chen L, McIntosh CM, Alegre ML. Exercise increases skin graft resistance to rejection. Am J Transplant. 2019 May; 19(5):1560-1567. View in: PubMed

  18. Alegre ML. B cells, CMV, and stem cell transplant. Science. 2019 01 18; 363(6424):232-233. View in: PubMed

  19. Owen DL, Mahmud SA, Sjaastad LE, Williams JB, Spanier JA, Simeonov DR, Ruscher R, Huang W, Proekt I, Miller CN, Hekim C, Jeschke JC, Aggarwal P, Broeckel U, LaRue RS, Henzler CM, Alegre ML, Anderson MS, August A, Marson A, Zheng Y, Williams CB, Farrar MA. Thymic regulatory T cells arise via two distinct developmental programs. Nat Immunol. 2019 02; 20(2):195-205. View in: PubMed

  20. Alegre ML. The Importance of Inflammation-induced NETS. Am J Transplant. 2019 Jan; 19(1):3. View in: PubMed

  21. Wu Q, Turturice B, Wagner S, Huang Y, Gupta PK, Schott C, Metwally A, Ranjan R, Perkins D, Alegre ML, Finn P, Budinger GRS, Shilling R, Bharat A. Gut Microbiota Can Impact Chronic Murine Lung Allograft Rejection. Am J Respir Cell Mol Biol. 2019 Jan; 60(1):131-134. View in: PubMed

  22. Gupta PK, Alegre ML. Th17 Cells Changing Colors. Am J Transplant. 2018 Dec; 18(12):2841. View in: PubMed

  23. Alegre ML. Creating a Niche. Am J Transplant. 2018 Nov; 18(11):2617. View in: PubMed

  24. Alegre ML. Danger, Metabolism and T Cell Memory. Am J Transplant. 2018 Oct; 18(10):2375. View in: PubMed

  25. Alegre ML. The Adaptive NK Cell Response. Am J Transplant. 2018 Sep; 18(9):2105. View in: PubMed

  26. Miller ML, McIntosh CM, Williams JB, Wang Y, Hollinger MK, Isaad NJ, Moon JJ, Gajewski TF, Chong AS, Alegre ML. Distinct Graft-Specific TCR Avidity Profiles during Acute Rejection and Tolerance. Cell Rep. 2018 08 21; 24(8):2112-2126. View in: PubMed

  27. Mcintosh CM, Alegre ML. Metabolic Control of T Cell Memory. Am J Transplant. 2018 Aug; 18(8):1835. View in: PubMed

  28. Alegre ML. Preventing PTLD? Am J Transplant. 2018 Jul; 18(7):1583. View in: PubMed

  29. Young JS, Yin D, Vannier AGL, Alegre ML, Chong AS. Equal Expansion of Endogenous Transplant-Specific Regulatory T Cell and Recruitment Into the Allograft During Rejection and Tolerance. Front Immunol. 2018; 9:1385. View in: PubMed

  30. Alegre ML. A Cause for Leaky Guts. Am J Transplant. 2018 Jun; 18(6):1299. View in: PubMed

  31. McIntosh CM, Chen L, Shaiber A, Eren AM, Alegre ML. Gut microbes contribute to variation in solid organ transplant outcomes in mice. Microbiome. 2018 05 25; 6(1):96. View in: PubMed

  32. Alegre ML. Immune Regulation of Lung Fibrosis. Am J Transplant. 2018 May; 18(5):1039. View in: PubMed

  33. Tu E, Chia CPZ, Chen W, Zhang D, Park SA, Jin W, Wang D, Alegre ML, Zhang YE, Sun L, Chen W. T Cell Receptor-Regulated TGF-ß Type I Receptor Expression Determines T Cell Quiescence and Activation. Immunity. 2018 04 17; 48(4):745-759.e6. View in: PubMed

  34. Alegre ML. Sweet T Cell Dysfunction. Am J Transplant. 2018 Apr; 18(4):775. View in: PubMed

  35. Alegre ML. Mind the GAP, for Tolerance to Gut Bacteria. Am J Transplant. 2018 Mar; 18(3):533. View in: PubMed

  36. Alegre ML. DC Metabolism Controls Lung T Cell Polarization. Am J Transplant. 2018 02; 18(2):285. View in: PubMed

  37. Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre ML, Luke JJ, Gajewski TF. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. 2018 01 05; 359(6371):104-108. View in: PubMed

  38. Riella LV, Alegre ML. Novel Role of Calcineurin Inhibitors in Curbing T Cells' Sweet Tooth. Am J Transplant. 2018 Jan; 18(1):3. View in: PubMed

  39. Alegre ML. What's new in transplantation tolerance? Curr Opin Organ Transplant. 2018 02; 23(1):63-65. View in: PubMed

  40. Alegre ML. Stealing Tregs' Identity (by Deleting NF-?B). Am J Transplant. 2017 Dec; 17(12):2997. View in: PubMed

  41. Alegre ML. Making Therapeutic Antibodies in Vitro. Am J Transplant. 2017 Nov; 17(11):2753. View in: PubMed

  42. Young JS, Khiew SH, Yang J, Vannier A, Yin D, Sciammas R, Alegre ML, Chong AS. Successful Treatment of T Cell-Mediated Acute Rejection with Delayed CTLA4-Ig in Mice. Front Immunol. 2017; 8:1169. View in: PubMed

  43. Alegre ML. Predicting TCR specificity? Am J Transplant. 2017 Oct; 17(10):2501. View in: PubMed

  44. Alegre ML. The Unbearable Lightness of Breathing. Am J Transplant. 2017 Sep; 17(9):2233. View in: PubMed

  45. Azzi J, Raimondi G, Mas V, Riella LV, Elfadawy N, Safa K, Wojciechowski D, Kanak M, Nog R, Maltzman JS, Ford ML, Pober JS, Luo XR, Rothstein D, Miller ML, Matthews D, Burlingham W, Levings M, Heeger P, Higdon L, Gill J, Gill RG, Alegre ML. The outstanding questions in transplantation: It's about time…. Am J Transplant. 2018 01; 18(1):271-272. View in: PubMed

  46. Alegre ML. Immune-Electrical Connection. Am J Transplant. 2017 Aug; 17(8):1965. View in: PubMed

  47. Alegre ML. The Bugs That Keep Us Safe. Am J Transplant. 2017 Jul; 17(7):1699. View in: PubMed

  48. Young JS, McIntosh C, Alegre ML, Chong AS. Evolving Approaches in the Identification of Allograft-Reactive T and B Cells in Mice and Humans. Transplantation. 2017 11; 101(11):2671-2681. View in: PubMed

  49. Alegre ML. Timing Is Everything. Am J Transplant. 2017 Jun; 17(6):1433. View in: PubMed

  50. Alegre ML. Select Effects of IL-13 in Driving Tissue Repair and Fibrosis. Am J Transplant. 2016 Oct; 16(10):2771. View in: PubMed

  51. Riella LV, Bagley J, Iacomini J, Alegre ML. Impact of environmental factors on alloimmunity and transplant fate. J Clin Invest. 2017 Jun 30; 127(7):2482-2491. View in: PubMed

  52. Khiew SH, Yang J, Young JS, Chen J, Wang Q, Yin D, Vu V, Miller ML, Sciammas R, Alegre ML, Chong AS. CTLA4-Ig in combination with FTY720 promotes allograft survival in sensitized recipients. JCI Insight. 2017 May 04; 2(9). View in: PubMed

  53. Alegre ML. Anti-Inflammatory Effects of Nonprofessional Phagocyte. Am J Transplant. 2017 May; 17(5):1151. View in: PubMed

  54. Alegre ML. The Tpm Subset of the CD8+ T Cell Memory Family. Am J Transplant. 2017 Apr; 17(4):849. View in: PubMed

  55. Alegre ML. Ionic Checkpoint: Potassium-Driven T Cell Immunosuppression. Am J Transplant. 2016 Dec; 16(12):3313. View in: PubMed

  56. Alegre ML. Dendritic Cell Identification for Dummies. Am J Transplant. 2017 Mar; 17(3):593. View in: PubMed

  57. Alegre ML. The Multiple Molecular Paths of Antibody Suppression by TFR Cells. Am J Transplant. 2017 Feb; 17(2):311. View in: PubMed

  58. Miller ML, Alegre ML. Super-MANF to the Rescue: Immunomodulation Improves Retinal Repair and Regenerative Cell Therapy. Am J Transplant. 2017 Jan; 17(1):3. View in: PubMed

  59. Miller ML, Alegre ML, Chong AS. Transplantation tolerance after allograft rejection. Curr Opin Organ Transplant. 2017 Feb; 22(1):64-70. View in: PubMed

  60. Alegre ML, McNerney ME. Natural killer cell subsets in allograft rejection and tolerance. Curr Opin Organ Transplant. 2007 Feb; 12(1):10-16. View in: PubMed

  61. Alegre ML, Lakkis FG, Morelli AE. Antigen Presentation in Transplantation. Trends Immunol. 2016 12; 37(12):831-843. View in: PubMed

  62. Alegre ML. Standardizing Mouse Models to Account for Host-Microbial Interactions. Am J Transplant. 2016 Sep; 16(9):2503. View in: PubMed

  63. Alegre ML, Chen L, David MZ, Bartman C, Boyle-Vavra S, Kumar N, Chong AS, Daum RS. Impact of Staphylococcus aureus USA300 Colonization and Skin Infections on Systemic Immune Responses in Humans. J Immunol. 2016 08 15; 197(4):1118-26. View in: PubMed

  64. Lei YM, Chen L, Wang Y, Stefka AT, Molinero LL, Theriault B, Aquino-Michaels K, Sivan AS, Nagler CR, Gajewski TF, Chong AS, Bartman C, Alegre ML. The composition of the microbiota modulates allograft rejection. J Clin Invest. 2016 07 01; 126(7):2736-44. View in: PubMed

  65. Arina A, Idel C, Hyjek EM, Alegre ML, Wang Y, Bindokas VP, Weichselbaum RR, Schreiber H. Tumor-associated fibroblasts predominantly come from local and not circulating precursors. Proc Natl Acad Sci U S A. 2016 07 05; 113(27):7551-6. View in: PubMed

  66. Young JS, Daniels MD, Miller ML, Wang T, Zhong R, Yin D, Alegre ML, Chong AS. Erosion of Transplantation Tolerance After Infection. Am J Transplant. 2017 01; 17(1):81-90. View in: PubMed

  67. Miller ML, Daniels MD, Wang T, Wang Y, Xu J, Yin D, Chong AS, Alegre ML. Tracking of TCR-Transgenic T Cells Reveals That Multiple Mechanisms Maintain Cardiac Transplant Tolerance in Mice. Am J Transplant. 2016 10; 16(10):2854-2864. View in: PubMed

  68. Alegre ML, Gajewski TF. Germ Warfare. Sci Am. 2016 Apr; 314(4):50. View in: PubMed

  69. Miller ML, Chen J, Daniels MD, McKeague MG, Wang Y, Yin D, Vu V, Chong AS, Alegre ML. Adoptive Transfer of Tracer-Alloreactive CD4+ T Cell Receptor Transgenic T Cells Alters the Endogenous Immune Response to an Allograft. Am J Transplant. 2016 10; 16(10):2842-2853. View in: PubMed

  70. Molinero LL, Yin D, Lei YM, Chen L, Wang Y, Chong AS, Alegre ML. High-Fat Diet-Induced Obesity Enhances Allograft Rejection. Transplantation. 2016 05; 100(5):1015-21. View in: PubMed

  71. Young JS, Chen J, Miller ML, Vu V, Tian C, Moon JJ, Alegre ML, Sciammas R, Chong AS. Delayed Cytotoxic T Lymphocyte-Associated Protein 4-Immunoglobulin Treatment Reverses Ongoing Alloantibody Responses and Rescues Allografts From Acute Rejection. Am J Transplant. 2016 08; 16(8):2312-23. View in: PubMed

  72. Evaristo C, Spranger S, Barnes SE, Miller ML, Molinero LL, Locke FL, Gajewski TF, Alegre ML. Cutting Edge: Engineering Active IKKß in T Cells Drives Tumor Rejection. J Immunol. 2016 Apr 01; 196(7):2933-8. View in: PubMed

  73. Theriault B, Wang Y, Chen L, Vest A, Bartman C, Alegre ML. Long-term Maintenance of Sterility Following Skin Transplantation in Germ-free Mice. Transplant Direct. 2015 Sep; 1(8). View in: PubMed

  74. Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, Benyamin FW, Lei YM, Jabri B, Alegre ML, Chang EB, Gajewski TF. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015 Nov 27; 350(6264):1084-9. View in: PubMed

  75. Zhao F, Cheng BL, Boyle-Vavra S, Alegre ML, Daum RS, Chong AS, Montgomery CP. Proteomic Identification of saeRS-Dependent Targets Critical for Protective Humoral Immunity against Staphylococcus aureus Skin Infection. Infect Immun. 2015 Sep; 83(9):3712-21. View in: PubMed

  76. Miller ML, Daniels MD, Wang T, Chen J, Young J, Xu J, Wang Y, Yin D, Vu V, Husain AN, Alegre ML, Chong AS. Spontaneous restoration of transplantation tolerance after acute rejection. Nat Commun. 2015 Jul 07; 6:7566. View in: PubMed

  77. Xu Y, Evaristo C, Alegre ML, Gurbuxani S, Kee BL. Analysis of GzmbCre as a Model System for Gene Deletion in the Natural Killer Cell Lineage. PLoS One. 2015; 10(4):e0125211. View in: PubMed

  78. Barnes SE, Wang Y, Chen L, Molinero LL, Gajewski TF, Evaristo C, Alegre ML. T cell-NF-?B activation is required for tumor control in vivo. J Immunother Cancer. 2015; 3(1):1. View in: PubMed

  79. Alegre ML. I spy alloreactive T cells. Sci Transl Med. 2015 Jan 28; 7(272):272fs3. View in: PubMed

  80. Bartman C, Chong AS, Alegre ML. The influence of the microbiota on the immune response to transplantation. Curr Opin Organ Transplant. 2015 Feb; 20(1):1-7. View in: PubMed

  81. Woo SR, Fuertes MB, Corrales L, Spranger S, Furdyna MJ, Leung MY, Duggan R, Wang Y, Barber GN, Fitzgerald KA, Alegre ML, Gajewski TF. STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. Immunity. 2014 Nov 20; 41(5):830-42. View in: PubMed

  82. Lei YM, Nair L, Alegre ML. The interplay between the intestinal microbiota and the immune system. Clin Res Hepatol Gastroenterol. 2015 Feb; 39(1):9-19. View in: PubMed

  83. Alegre ML, Mannon RB, Mannon PJ. The microbiota, the immune system and the allograft. Am J Transplant. 2014 Jun; 14(6):1236-48. View in: PubMed

  84. Miller ML, Mashayekhi M, Chen L, Zhou P, Liu X, Michelotti M, Tramontini Gunn N, Powers S, Zhu X, Evaristo C, Alegre ML, Molinero LL. Basal NF-?B controls IL-7 responsiveness of quiescent naïve T cells. Proc Natl Acad Sci U S A. 2014 May 20; 111(20):7397-402. View in: PubMed

  85. Montgomery CP, Daniels M, Zhao F, Alegre ML, Chong AS, Daum RS. Protective immunity against recurrent Staphylococcus aureus skin infection requires antibody and interleukin-17A. Infect Immun. 2014 May; 82(5):2125-34. View in: PubMed

  86. Chong AS, Alegre ML. Transplantation tolerance and its outcome during infections and inflammation. Immunol Rev. 2014 Mar; 258(1):80-101. View in: PubMed

  87. Chong AS, Alegre ML, Miller ML, Fairchild RL. Lessons and limits of mouse models. Cold Spring Harb Perspect Med. 2013 Dec 01; 3(12):a015495. View in: PubMed

  88. Evaristo C, Alegre ML. IFN-?: The Dr. Jekyll and Mr. Hyde of immunology? Am J Transplant. 2013 Dec; 13(12):3057-8. View in: PubMed

  89. Alegre ML, Bartman C, Chong AS. Microbes and allogeneic transplantation. Transplantation. 2014 Jan 15; 97(1):5-11. View in: PubMed

  90. Molinero LL, Cubre A, Mora-Solano C, Wang Y, Alegre ML. T cell receptor/CARMA1/NF-?B signaling controls T-helper (Th) 17 differentiation. Proc Natl Acad Sci U S A. 2012 Nov 06; 109(45):18529-34. View in: PubMed

  91. Alegre ML, Bromberg JS, Bromberg JS. Commensal microbiota determine intestinal iTreg. Am J Transplant. 2012 Aug; 12(8):1967. View in: PubMed

  92. Alegre ML, Molinero LL. The inside story of dendritic cell immunotherapy. Am J Transplant. 2012 Jun; 12(6):1363-4. View in: PubMed

  93. Chong AS, Alegre ML. The impact of infection and tissue damage in solid-organ transplantation. Nat Rev Immunol. 2012 May 25; 12(6):459-71. View in: PubMed

  94. Porras DL, Wang Y, Zhou P, Molinero LL, Alegre ML. Role of T-cell-specific nuclear factor ?B in islet allograft rejection. Transplantation. 2012 May 27; 93(10):976-82. View in: PubMed

  95. Alegre ML, Bromberg JS. Literature watch implications for transplantation. The anti-infectious role of the IL-17 pathway. Am J Transplant. 2012 Jan; 12(1):3. View in: PubMed

  96. Alegre ML, Chong AS. "Tip-toeing" to an assay for transplantation tolerance? Am J Transplant. 2012 Mar; 12(3):519-20. View in: PubMed

  97. Molinero LL, Alegre ML. Role of T cell-nuclear factor ?B in transplantation. Transplant Rev (Orlando). 2012 Jul; 26(3):189-200. View in: PubMed

  98. Alegre ML, Fu YX. Attenuation by targeting the B- and T-cell attenuator. Transplantation. 2011 Nov 27; 92(10):1075-6. View in: PubMed

  99. Ahmed EB, Wang T, Daniels M, Alegre ML, Chong AS. IL-6 induced by Staphylococcus aureus infection prevents the induction of skin allograft acceptance in mice. Am J Transplant. 2011 May; 11(5):936-46. View in: PubMed

  100. Molinero LL, Miller ML, Evaristo C, Alegre ML. High TCR stimuli prevent induced regulatory T cell differentiation in a NF-?B-dependent manner. J Immunol. 2011 Apr 15; 186(8):4609-17. View in: PubMed

  101. Ahmed EB, Daniels M, Alegre ML, Chong AS. Bacterial infections, alloimmunity, and transplantation tolerance. Transplant Rev (Orlando). 2011 Jan; 25(1):27-35. View in: PubMed

  102. Wang T, Ahmed EB, Chen L, Xu J, Tao J, Wang CR, Alegre ML, Chong AS. Infection with the intracellular bacterium, Listeria monocytogenes, overrides established tolerance in a mouse cardiac allograft model. Am J Transplant. 2010 Jul; 10(7):1524-33. View in: PubMed

  103. Bhorade SM, Chen H, Molinero L, Liao C, Garrity ER, Vigneswaran WT, Shilling R, Sperling A, Chong A, Alegre ML. Decreased percentage of CD4+FoxP3+ cells in bronchoalveolar lavage from lung transplant recipients correlates with development of bronchiolitis obliterans syndrome. Transplantation. 2010 Sep 15; 90(5):540-6. View in: PubMed

  104. Ahmed EB, Alegre ML, Chong AS. Role of bacterial infections in allograft rejection. Expert Rev Clin Immunol. 2008 Mar; 4(2):281-93. View in: PubMed

  105. Sweiss NJ, Salloum R, Gandhi S, Ghandi S, Alegre ML, Sawaqed R, Badaracco M, Pursell K, Pitrak D, Baughman RP, Moller DR, Garcia JG, Niewold TB. Significant CD4, CD8, and CD19 lymphopenia in peripheral blood of sarcoidosis patients correlates with severe disease manifestations. PLoS One. 2010 Feb 05; 5(2):e9088. View in: PubMed

  106. Alegre ML, Chong A. Toll-like receptors (TLRs) in transplantation. Front Biosci (Elite Ed). 2009 Jun 01; 1:36-43. View in: PubMed

  107. Molinero LL, Yang J, Gajewski T, Abraham C, Farrar MA, Alegre ML. CARMA1 controls an early checkpoint in the thymic development of FoxP3+ regulatory T cells. J Immunol. 2009 Jun 01; 182(11):6736-43. View in: PubMed

  108. Alegre ML, Chen L, Wang T, Ahmed E, Wang CR, Chong A. Antagonistic effect of toll-like receptor signaling and bacterial infections on transplantation tolerance. Transplantation. 2009 May 15; 87(9 Suppl):S77-9. View in: PubMed

  109. Chen L, Ahmed E, Wang T, Wang Y, Ochando J, Chong AS, Alegre ML. TLR signals promote IL-6/IL-17-dependent transplant rejection. J Immunol. 2009 May 15; 182(10):6217-25. View in: PubMed

  110. Molinero LL, Wang Y, Zhou P, Yagita H, Alegre ML. Fas mediates cardiac allograft acceptance in mice with impaired T-cell-intrinsic NF-kappaB signaling. Transpl Int. 2009 Aug; 22(8):845-52. View in: PubMed

  111. O'Neill SK, Veselits ML, Zhang M, Labno C, Cao Y, Finnegan A, Uccellini M, Alegre ML, Cambier JC, Clark MR. Endocytic sequestration of the B cell antigen receptor and toll-like receptor 9 in anergic cells. Proc Natl Acad Sci U S A. 2009 Apr 14; 106(15):6262-7. View in: PubMed

  112. Song J, Volkov S, Shea CR, Alegre ML, Salgia R, Gregg K, Curran JJ, Woodruff J, Krausz T, Levine JS, Sweiss NJ. Nephrogenic systemic fibrosis associated with stromal and vascular calcification, report of two cases. J Cutan Pathol. 2009 Oct; 36 Suppl 1:31-4. View in: PubMed

  113. Zimmer MI, Nguyen HP, Wang B, Xu H, Colmone A, Felio K, Choi HJ, Zhou P, Alegre ML, Wang CR. Polymorphisms in CD1d affect antigen presentation and the activation of CD1d-restricted T cells. Proc Natl Acad Sci U S A. 2009 Feb 10; 106(6):1909-14. View in: PubMed

  114. Alegre ML, Goldstein DR, Chong AS. Toll-like receptor signaling in transplantation. Curr Opin Organ Transplant. 2008 Aug; 13(4):358-65. View in: PubMed

  115. Alegre ML, Leemans J, Le Moine A, Florquin S, De Wilde V, Chong A, Goldman M. The multiple facets of toll-like receptors in transplantation biology. Transplantation. 2008 Jul 15; 86(1):1-9. View in: PubMed

  116. Wang T, Chen L, Ahmed E, Ma L, Yin D, Zhou P, Shen J, Xu H, Wang CR, Alegre ML, Chong AS. Prevention of allograft tolerance by bacterial infection with Listeria monocytogenes. J Immunol. 2008 May 01; 180(9):5991-9. View in: PubMed

  117. Qiao G, Li Z, Molinero L, Alegre ML, Ying H, Sun Z, Penninger JM, Zhang J. T-cell receptor-induced NF-kappaB activation is negatively regulated by E3 ubiquitin ligase Cbl-b. Mol Cell Biol. 2008 Apr; 28(7):2470-80. View in: PubMed

  118. Chen L, Hussien Y, Hwang KW, Wang Y, Zhou P, Alegre ML. Overexpression of program death-1 in T cells has mild impact on allograft survival. Transpl Int. 2008 Jan; 21(1):21-9. View in: PubMed

  119. Molinero LL, Zhou P, Wang Y, Harlin H, Kee B, Abraham C, Alegre ML. Epidermal Langerhans cells promote skin allograft rejection in mice with NF-kappa B-impaired T cells. Am J Transplant. 2008 Jan; 8(1):21-31. View in: PubMed

  120. Alegre ML, Florquin S, Goldman M. Cellular mechanisms underlying acute graft rejection: time for reassessment. Curr Opin Immunol. 2007 Oct; 19(5):563-8. View in: PubMed

  121. Vilimas T, Mascarenhas J, Palomero T, Mandal M, Buonamici S, Meng F, Thompson B, Spaulding C, Macaroun S, Alegre ML, Kee BL, Ferrando A, Miele L, Aifantis I. Targeting the NF-kappaB signaling pathway in Notch1-induced T-cell leukemia. Nat Med. 2007 Jan; 13(1):70-7. View in: PubMed

  122. Alegre ML, Najafian N. Costimulatory molecules as targets for the induction of transplantation tolerance. Curr Mol Med. 2006 Dec; 6(8):843-57. View in: PubMed

  123. Chen L, Wang T, Zhou P, Ma L, Yin D, Shen J, Molinero L, Nozaki T, Phillips T, Uematsu S, Akira S, Wang CR, Fairchild RL, Alegre ML, Chong A. TLR engagement prevents transplantation tolerance. Am J Transplant. 2006 Oct; 6(10):2282-91. View in: PubMed

  124. McNerney ME, Lee KM, Zhou P, Molinero L, Mashayekhi M, Guzior D, Sattar H, Kuppireddi S, Wang CR, Kumar V, Alegre ML. Role of natural killer cell subsets in cardiac allograft rejection. Am J Transplant. 2006 Mar; 6(3):505-13. View in: PubMed

  125. Alegre ML, Fallarino F. Mechanisms of CTLA-4-Ig in tolerance induction. Curr Pharm Des. 2006; 12(2):149-60. View in: PubMed

  126. Lo JC, Basak S, James ES, Quiambo RS, Kinsella MC, Alegre ML, Weih F, Franzoso G, Hoffmann A, Fu YX. Coordination between NF-kappaB family members p50 and p52 is essential for mediating LTbetaR signals in the development and organization of secondary lymphoid tissues. Blood. 2006 Feb 01; 107(3):1048-55. View in: PubMed

  127. Zhou P, Balin SJ, Mashayekhi M, Hwang KW, Palucki DA, Alegre ML. Transplantation tolerance in NF-kappaB-impaired mice is not due to regulation but is prevented by transgenic expression of Bcl-xL. J Immunol. 2005 Mar 15; 174(6):3447-53. View in: PubMed

  128. Brown IE, Mashayekhi M, Markiewicz M, Alegre ML, Gajewski TF. Peripheral survival of naïve CD8+ T cells. Apoptosis. 2005 Jan; 10(1):5-11. View in: PubMed

  129. Subudhi SK, Alegre ML, Fu YX. The balance of immune responses: costimulation verse coinhibition. J Mol Med (Berl). 2005 Mar; 83(3):193-202. View in: PubMed

  130. Li D, Gál I, Vermes C, Alegre ML, Chong AS, Chen L, Shao Q, Adarichev V, Xu X, Koreny T, Mikecz K, Finnegan A, Glant TT, Zhang J. Cutting edge: Cbl-b: one of the key molecules tuning CD28- and CTLA-4-mediated T cell costimulation. J Immunol. 2004 Dec 15; 173(12):7135-9. View in: PubMed

  131. Hwang KW, Sweatt WB, Mashayekhi M, Palucki DA, Sattar H, Chuang E, Alegre ML. Transgenic expression of CTLA-4 controls lymphoproliferation in IL-2-deficient mice. J Immunol. 2004 Nov 01; 173(9):5415-24. View in: PubMed

  132. O'Keefe JP, Blaine K, Alegre ML, Gajewski TF. Formation of a central supramolecular activation cluster is not required for activation of naive CD8+ T cells. Proc Natl Acad Sci U S A. 2004 Jun 22; 101(25):9351-6. View in: PubMed

  133. Subudhi SK, Zhou P, Yerian LM, Chin RK, Lo JC, Anders RA, Sun Y, Chen L, Wang Y, Alegre ML, Fu YX. Local expression of B7-H1 promotes organ-specific autoimmunity and transplant rejection. J Clin Invest. 2004 Mar; 113(5):694-700. View in: PubMed

  134. Rivas FV, O'Keefe JP, Alegre ML, Gajewski TF. Actin cytoskeleton regulates calcium dynamics and NFAT nuclear duration. Mol Cell Biol. 2004 Feb; 24(4):1628-39. View in: PubMed

  135. Fallarino F, Grohmann U, Hwang KW, Orabona C, Vacca C, Bianchi R, Belladonna ML, Fioretti MC, Alegre ML, Puccetti P. Modulation of tryptophan catabolism by regulatory T cells. Nat Immunol. 2003 Dec; 4(12):1206-12. View in: PubMed

  136. Kaufman CK, Zhou P, Pasolli HA, Rendl M, Bolotin D, Lim KC, Dai X, Alegre ML, Fuchs E. GATA-3: an unexpected regulator of cell lineage determination in skin. Genes Dev. 2003 Sep 01; 17(17):2108-22. View in: PubMed

  137. Zhou P, Hwang KW, Palucki D, Kim O, Newell KA, Fu YX, Alegre ML. Secondary lymphoid organs are important but not absolutely required for allograft responses. Am J Transplant. 2003 Mar; 3(3):259-66. View in: PubMed

  138. Zhou P, Hwang KW, Palucki DA, Guo Z, Boothby M, Newell KA, Alegre ML. Impaired NF-kappaB activation in T cells permits tolerance to primary heart allografts and to secondary donor skin grafts. Am J Transplant. 2003 Feb; 3(2):139-47. View in: PubMed

  139. Tang Q, Smith JA, Szot GL, Zhou P, Alegre ML, Henriksen KJ, Thompson CB, Bluestone JA. CD28/B7 regulation of anti-CD3-mediated immunosuppression in vivo. J Immunol. 2003 Feb 01; 170(3):1510-6. View in: PubMed

  140. Utset TO, Auger JA, Peace D, Zivin RA, Xu D, Jolliffe L, Alegre ML, Bluestone JA, Clark MR. Modified anti-CD3 therapy in psoriatic arthritis: a phase I/II clinical trial. J Rheumatol. 2002 Sep; 29(9):1907-13. View in: PubMed

  141. Harlin H, Hwang KW, Palucki DA, Kim O, Thompson CB, Boothby M, Alegre ML. CTLA-4 engagement regulates NF-kappaB activation in vivo. Eur J Immunol. 2002 Aug; 32(8):2095-104. View in: PubMed

  142. Harlin H, Podack E, Boothby M, Alegre ML. TCR-independent CD30 signaling selectively induces IL-13 production via a TNF receptor-associated factor/p38 mitogen-activated protein kinase-dependent mechanism. J Immunol. 2002 Sep 01; 169(5):2451-9. View in: PubMed

  143. Hwang KW, Sweatt WB, Brown IE, Blank C, Gajewski TF, Bluestone JA, Alegre ML. Cutting edge: targeted ligation of CTLA-4 in vivo by membrane-bound anti-CTLA-4 antibody prevents rejection of allogeneic cells. J Immunol. 2002 Jul 15; 169(2):633-7. View in: PubMed

  144. Szot GL, Zhou P, Rulifson I, Wang J, Guo Z, Kim O, Newel KA, Thistlethwaite JR, Bluestone JA, Alegre ML. Different mechanisms of cardiac allograft rejection in wildtype and CD28-deficient mice. Am J Transplant. 2001 May; 1(1):38-46. View in: PubMed

  145. Alegre ML, Frauwirth KA, Thompson CB. T-cell regulation by CD28 and CTLA-4. Nat Rev Immunol. 2001 Dec; 1(3):220-8. View in: PubMed

  146. Guo Z, Meng L, Kim O, Wang J, Hart J, He G, Alegre ML, Thistlethwaite JR, Pearson TC, Larsen CP, Newell KA. CD8 T cell-mediated rejection of intestinal allografts is resistant to inhibition of the CD40/CD154 costimulatory pathway. Transplantation. 2001 May 15; 71(9):1351-4. View in: PubMed

  147. Zhou P, Szot G, Guo Z, Kim O, He G, Wang J, Grusby M, Newell K, Thistlethwaite J, Bluestone J, Alegre M. Role of STAT6 signaling in the induction and long-term maintenance of tolerance mediated by CTLA4-Ig. Transplant Proc. 2001 Feb-Mar; 33(1-2):214-6. View in: PubMed

  148. Alegre M, Fallarino F, Zhou P, Frauwirth K, Thistlethwaite J, Newell K, Gajewski T, Bluestone J. Transplantation and the CD28/CTLA4/B7 pathway. Transplant Proc. 2001 Feb-Mar; 33(1-2):209-11. View in: PubMed

  149. Gajewski TF, Fallarino F, Fields PE, Rivas F, Alegre ML. Absence of CTLA-4 lowers the activation threshold of primed CD8+ TCR-transgenic T cells: lack of correlation with Src homology domain 2-containing protein tyrosine phosphatase. J Immunol. 2001 Mar 15; 166(6):3900-7. View in: PubMed

  150. Kouki T, Sawai Y, Gardine CA, Fisfalen ME, Alegre ML, DeGroot LJ. CTLA-4 gene polymorphism at position 49 in exon 1 reduces the inhibitory function of CTLA-4 and contributes to the pathogenesis of Graves' disease. J Immunol. 2000 Dec 01; 165(11):6606-11. View in: PubMed

  151. Zhou P, Szot GL, Guo Z, Kim O, He G, Wang J, Grusby MJ, Newell KA, Thistlethwaite JR, Bluestone JA, Alegre ML. Role of STAT4 and STAT6 signaling in allograft rejection and CTLA4-Ig-mediated tolerance. J Immunol. 2000 Nov 15; 165(10):5580-7. View in: PubMed

  152. Alegre ML. Costimulatory molecules as targets for the induction of transplantation tolerance. Nephrol Dial Transplant. 1999 Feb; 14(2):322-32. View in: PubMed

  153. Chuang E, Lee KM, Robbins MD, Duerr JM, Alegre ML, Hambor JE, Neveu MJ, Bluestone JA, Thompson CB. Regulation of cytotoxic T lymphocyte-associated molecule-4 by Src kinases. J Immunol. 1999 Feb 01; 162(3):1270-7. View in: PubMed

  154. Mandal M, Chen XR, Alegre ML, Chiu NM, Chen YH, Castaño AR, Wang CR. Tissue distribution, regulation and intracellular localization of murine CD1 molecules. Mol Immunol. 1998 Jun; 35(9):525-36. View in: PubMed

  155. Alegre ML, Shiels H, Thompson CB, Gajewski TF. Expression and function of CTLA-4 in Th1 and Th2 cells. J Immunol. 1998 Oct 01; 161(7):3347-56. View in: PubMed

  156. Noel PJ, Alegre ML, Reiner SL, Thompson CB. Impaired negative selection in CD28-deficient mice. Cell Immunol. 1998 Aug 01; 187(2):131-8. View in: PubMed

  157. Lin H, Rathmell JC, Gray GS, Thompson CB, Leiden JM, Alegre ML. Cytotoxic T lymphocyte antigen 4 (CTLA4) blockade accelerates the acute rejection of cardiac allografts in CD28-deficient mice: CTLA4 can function independently of CD28. J Exp Med. 1998 Jul 06; 188(1):199-204. View in: PubMed

  158. Chuang E, Alegre ML, Duckett CS, Noel PJ, Vander Heiden MG, Thompson CB. Interaction of CTLA-4 with the clathrin-associated protein AP50 results in ligand-independent endocytosis that limits cell surface expression. J Immunol. 1997 Jul 01; 159(1):144-51. View in: PubMed

  159. Alegre ML, Noel PJ, Eisfelder BJ, Chuang E, Clark MR, Reiner SL, Thompson CB. Regulation of surface and intracellular expression of CTLA4 on mouse T cells. J Immunol. 1996 Dec 01; 157(11):4762-70. View in: PubMed

  160. Cozzi PJ, Padrid P, Tompkins MB, Alegre ML, Takeda J, Leff AR. Bioactivity of recombinant feline interleukin-2 on human and feline leukocytes. Vet Immunol Immunopathol. 1995 Sep; 48(1-2):27-33. View in: PubMed

  161. Cozzi PJ, Padrid PA, Takeda J, Alegre ML, Yuhki N, Leff AR. Sequence and functional characterization of feline interleukin 2. Biochem Biophys Res Commun. 1993 Aug 16; 194(3):1038-43. View in: PubMed

  162. Alegre ML, Peterson LJ, Jeyarajah DR, Weiser M, Bluestone JA, Thistlethwaite JR. Severe combined immunodeficient mice engrafted with human splenocytes have functional human T cells and reject human allografts. J Immunol. 1994 Sep 15; 153(6):2738-49. View in: PubMed

  163. Alegre ML, Sattar HA, Herold KC, Smith J, Tepper MA, Bluestone JA. Prevention of the humoral response induced by an anti-CD3 monoclonal antibody by deoxyspergualin in a murine model. Transplantation. 1994 Jun 27; 57(12):1786-94. View in: PubMed

  164. Alegre ML, Peterson LJ, Xu D, Sattar HA, Jeyarajah DR, Kowalkowski K, Thistlethwaite JR, Zivin RA, Jolliffe L, Bluestone JA. A non-activating "humanized" anti-CD3 monoclonal antibody retains immunosuppressive properties in vivo. Transplantation. 1994 Jun 15; 57(11):1537-43. View in: PubMed

  165. Alegre ML, Lenschow DJ, Bluestone JA. Immunomodulation of transplant rejection using monoclonal antibodies and soluble receptors. Dig Dis Sci. 1995 Jan; 40(1):58-64. View in: PubMed

  166. Alegre ML, Tso JY, Sattar HA, Smith J, Desalle F, Cole M, Bluestone JA. An anti-murine CD3 monoclonal antibody with a low affinity for Fc gamma receptors suppresses transplantation responses while minimizing acute toxicity and immunogenicity. J Immunol. 1995 Aug 01; 155(3):1544-55. View in: PubMed

  167. Alegre ML, Collins AM, Pulito VL, Brosius RA, Olson WC, Zivin RA, Knowles R, Thistlethwaite JR, Jolliffe LK, Bluestone JA. Effect of a single amino acid mutation on the activating and immunosuppressive properties of a "humanized" OKT3 monoclonal antibody. J Immunol. 1992 Jun 01; 148(11):3461-8. View in: PubMed

  168. Woodle ES, Thistlethwaite JR, Jolliffe LK, Zivin RA, Collins A, Adair JR, Bodmer M, Athwal D, Alegre ML, Bluestone JA. Humanized OKT3 antibodies: successful transfer of immune modulating properties and idiotype expression. J Immunol. 1992 May 01; 148(9):2756-63. View in: PubMed