Adoptive Transfer of Tracer-Alloreactive CD4⁺ T Cell Receptor Transgenic T Cells Alters the Endogenous Immune...

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 CD4⁺ or CD8⁺ TCR-Tg or polyclonal T cells at the time of cardiac allograft transplantation. Only CD4⁺ 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 CD4⁺ TCR-Tg T cells exhibited enhanced endogenous donor-specific CD8⁺ T cell activation in the spleen and accelerated alloantibody production. Introduction of CD4⁺ TCR-Tg T cells also perturbed the intragraft accumulation of innate cell populations. Transferred CD4⁺ 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 CD4⁺ T cell immunotherapy in tumor and infectious clinical settings because cell infusion may have additional effects on natural immune responses.