In addition to the therapeutic use of adoptive transfer of T cells to combat viral infections and malignancies in humans, adoptive transfer of T cell receptor transgenic (TCR-Tg) cells is often used in mice to track a tracer population of antigen-specific T cells and extrapolate findings to endogenous responses. However, the effects of TCR-Tg cells on endogenous cell populations are not well known. In an acute rejection model using BALB/c cardiac allografts transplanted into C57Bl/6 recipients, animals were seeded with naive CD4⁺ T cells with a fixed TCR (TCR75) that recognizes a BALB/c MHC Class I peptide from K^d, presented on recipient MHC Class II I-A^b. The seeded TCR75 cells did take on the characteristics of polyclonal intra-graft CD4⁺ T cells analyzed in transplant recipients that did not receive T cell transfer. However, transfer of TCR75 cells modified the endogenous response in that endogenous CD4⁺ and CD8⁺ T cells from transferred recipients failed to accumulate in the graft and had reduced cytokine production compared to the TCR75 cells themselves and to T cells from non-transfer animals. Transfer of TCR75 cells also reduced the total numbers of antigen presenting cells infiltrating the grafts. In contrast, it induced a remarkable accumulation of intra-graft neutrophils. Results were similar with a second TCR-Tg CD4 T cell, TEa, that recognizes a BALB/c MHC Class II peptide from I-E^d presented on recipient MHC Class II I-A^b, but not with transfer of the same number of naive polyclonal T cells, suggesting that the effects are dependent on recognition of donor antigen by the transferred T cells. Thus, caution must be used in interpreting the behavior of cell populations in animals receiving adoptive transfer of TCR-Tg cells as the overall nature of the rejection may be altered by the presence of the transferred cells. Moreover, these results may have important implications for adoptive T cell immunotherapy in tumor and infectious clinical settings as T cell transfer may dampen or eliminate the natural endogenous T cell responses to tumor or microbial antigens.

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