Differential Requirement of CD27 Costimulatory Signaling for Naïve Versus Alloantigen‐Primed Effector/Memory CD8+ T Cells |
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Authors: | K Yamaura O Boenisch T Watanabe T Ueno V Vanguri J Yang K Tanaka I Guleria J Borst Y Zhai J W Kupiec‐Weglinski N Najafian |
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Institution: | 1. Transplantation Research Center, Brigham and Women's Hospital and Children's Hospital;2. K.Y. and O.B. contributed equally to this work and are cofirst authors.;3. Immunology Research Division, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA;4. Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands;5. Dumont‐UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA |
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Abstract: | CD8+ memory T cells endanger allograft survival by causing acute and chronic rejection and prevent tolerance induction. We explored the role of CD27:CD70 T‐cell costimulatory pathway in alloreactive CD8+/CD4+ T‐cell activation. CD27‐deficient (CD27?/?) and wild‐type (WT) B6 mice rejected BALB/c cardiac allografts at similar tempo, with or without depletion of CD4+ or CD8+ T cells, suggesting that CD27 is not essential during primary T‐cell alloimmune responses. To dissect the role of CD27 in primed effector and memory alloreactive T cells, CD27?/? or WT mice were challenged with BALB/c hearts either 10 or 40 days after sensitization with donor‐type skin grafts. Compared to WT controls, allograft survival was prolonged in day 40‐ but not day 10‐sensitized CD27?/? recipients. Improved allograft survival was accompanied by diminished secondary responsiveness of memory CD8+ T cells, which resulted from deficiency in memory formation rather than their lack of secondary expansion. Chronic allograft vasculopathy and fibrosis were diminished in CD27?/? recipients of class I‐ but not class II‐mismatched hearts as compared to WT controls. These data establish a novel role for CD27 as an important costimulatory molecule for alloreactive CD8+ memory T cells in acute and chronic allograft rejection. |
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Keywords: | CD8 CD4 costimulation memory T cells transplantation |
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