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Different Mechanisms of Cardiac Allograft Rejection in Wildtype and CD28‐deficient Mice
Author(s) -
Szot Gregory L.,
Zhou Ping,
Rulifson Ingrid,
Wang Jun,
Guo Zhong,
Kim Oliver,
Newell Kenneth A.,
Thistlethwaite J. Richard,
Bluestone Jeffrey A.,
Alegre MariaLuisa
Publication year - 2001
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1034/j.1600-6143.2001.010108.x
Subject(s) - cd28 , cd8 , medicine , wild type , adoptive cell transfer , t cell , immunology , cytotoxic t cell , cancer research , immune system , biology , in vitro , biochemistry , mutant , gene
Although CD28 blockade results in long‐term cardiac allograft survival in wildtype mice, CD28‐deficient mice effectively reject heart allografts. This study compared the mechanisms of allogeneic responses in wildtype and CD28‐deficient mice. Adoptive transfer of purified CD28‐deficient T cells into transplanted nude mice resulted in graft rejection. However, this model demonstrated that the allogeneic T cell function was severely impaired when compared with wildtype T cells, despite similar survival kinetics. Cardiac allograft rejection depended on both CD4 + and CD8 + T cell subsets in CD28‐deficient mice, whereas only CD4 + T cells were necessary in wildtype recipients. These results suggested that CD8 + T cells were more important in CD28‐deficient than wildtype mice. In addition to the CD8 + T cell requirement, allograft rejection in CD28‐deficient mice was dependent on a sustained presence of CD4 + T cells, whereas it only required the initial presence of CD4 + T cells in wildtype mice. Taken together, these data suggest that CD4 + T cells from CD28‐deficient mice have impaired responses to alloantigen in vivo , thus requiring long‐lasting cooperation with CD8 + T cell responses to facilitate graft rejection. These results may help to explain the failure to promote graft tolerance in some preclinical and clinical settings.