THE INTRAGRAFT CD8(-CELL RESPONSE IN RENAL-ALLOGRAFT REJECTION IN THEMOUSE() T)

To identify the role of donor class I alloantigens in regulating the C D8(+) T cell response to a kidney allograft, we analyzed and compared the CD8(+) infiltrate in kidney transplants from MHC class I(-)deficie nt (class I-) mouse donors and class I+ controls. One week after trans plantation, there was a prominent CD8(+) infiltrate in control allogra fts, whereas CD8(+) T cells were virtually absent in grafts from class I- donors. In class If allografts, infiltrating CD8(+) cells utilized a wide range of T cell receptor (TCR) V-beta families and their V-bet a usage was similar to that of the systemic CD8(+) population. However , there was a modest but significant overrepresentation of cells beari ng V(beta)8 in the graft compared with the spleen due to an expansion of CD8(+) V(beta)8.3(+) cells. This could be detected as early as 1 we ek and became more pronounced by 3 weeks after transplantation. In 3-w eek allografts, only 52% of CD8(+) cells expressed alpha beta TCR. Amo ng T cells isolated from class I+ grafts, the CD8(+) V(beta)8(+) cells demonstrated allospecific responses that were numerically larger than responses of the CD8(+) V(beta)8(-) population. In contrast to the ea rly (1 week) time point, significant numbers of CD8(+) cells could be isolated from class I- grafts by 3 weeks after transplantation and the ir V-beta repertoire resembled that seen in controls. While increasing numbers of CD8+ V(beta)8(+) were present in the class I- grafts at 3 weeks, this increase was not statistically significant. Thus, expressi on of class I alloantigens on a kidney graft plays an important role i n regulating the rate of accumulation of CD8(+) T cells in rejecting k idney grafts. However, the V-beta repertoire of the CD8(+) T cell infi ltrate is TCR V-beta largely determined by factors that are independen t of normal class I expression on the graft.