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Adoptive Transfer of Tracer‐Alloreactive CD 4 + T Cell Receptor Transgenic T Cells Alters the Endogenous Immune Response to an Allograft
Author(s) -
Miller M. L.,
Chen J.,
Daniels M. D.,
McKeague M. G.,
Wang Y.,
Yin D.,
Vu V.,
Chong A. S.,
Alegre M.L.
Publication year - 2016
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 - 10.1111/ajt.13821
Subject(s) - endogeny , adoptive cell transfer , immune system , medicine , immunology , microbiology and biotechnology , t cell , genetically modified mouse , receptor , transgene , biology , endocrinology , genetics , gene
T cell receptor transgenic ( TCR ‐Tg) T cells are often used as tracer populations of antigen‐specific responses to extrapolate findings to endogenous T cells. The extent to which TCR ‐Tg T cells behave purely as tracer cells or modify the endogenous immune response is not clear. To test the impact of TCR ‐Tg T cell transfer on endogenous alloimmunity, recipient mice were seeded with CD 4 + or CD 8 + TCR ‐Tg or polyclonal T cells at the time of cardiac allograft transplantation. Only CD 4 + TCR ‐Tg T cells accelerated rejection and, unexpectedly, led to a dose‐dependent decrease in both transferred and endogenous T cells infiltrating the graft. In contrast, recipients of CD 4 + TCR ‐Tg T cells exhibited enhanced endogenous donor‐specific CD 8 + T cell activation in the spleen and accelerated alloantibody production. Introduction of CD 4 + TCR ‐Tg T cells also perturbed the intragraft accumulation of innate cell populations. Transferred CD 4 + TCR ‐Tg T cells alter many aspects of endogenous alloimmunity, suggesting that caution should be used when interpreting experiments using these adoptively transferred cells because the overall nature of allograft rejection may be altered. These results also may have implications for adoptive CD 4 + T cell immunotherapy in tumor and infectious clinical settings because cell infusion may have additional effects on natural immune responses.