To identify the role of donor class I alloantigens in regulating the CD8+ T cell response to a kidney allograft, we analyzed and compared the CD8+ infiltrate in kidney transplants from MHC class I-deficient (class I- ) mouse donors and class I+ controls. One week after transplantation, there was a prominent CD8+ infiltrate in control allografts, whereas CD8+ T cells were virtually absent in grafts from class I- donors. In class I+ allografts, infiltrating CD8+ cells utilized a wide range oft cell receptor (TCR) V(β) families and their V(β) usage was similar to that of the systemic CD8+ population. However, there was a modest but significant overrepresentation of cells bearing V(β)8 in the graft compared with the spleen due to an expansion of CD8+ V(β)8.3+ cells. This could be detected as early as 1 week and became more pronounced by 3 weeks after transplantation. In 3-week allografts, only 52% of CD8+ cells expressed αβTCR. Among T cells isolated from class I+ grafts, the CD8+ V(β)8+ cells demonstrated allospecific responses that were numerically larger than responses of the CD8+ V(β)8- population. In contrast to the early (1 week) time point, significant numbers of CD8+ cells could be isolated from class I- grafts by 3 weeks after transplantation and their V(β) repertoire resembled that seen in controls. While increasing numbers of CD8+ V(β)8+ were present in the class I- grafts at 3 weeks, this increase was not statistically significant. Thus, expression of class I alloantigens on a kidney graft plays an important role in regulating the rate of accumulation of CD8+ T cells in rejecting kidney grafts. However, the TCR V, repertoire of the CD8+ T cell infiltrate is largely determined by factors that are independent of normal class I expression on the graft.
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