Recipient CD4 T regulatory cells inhibit the acute T cell-mediated rejection of renal allografts in wild-type mice. The survival of single class II MHC-disparate H-2bm12renal allografts was tested in B6.CCR5-/-recipients, which have defects in T regulatory cell activities that constrain alloimmune responses. In contrast to wild-type C57BL/6 recipients, B6.CCR5-/-recipients rejected the bm12 renal allografts. However, donor-reactive CD8 T cells rather than CD4 T cells were the primary effector T cells mediating rejection. The CD8 T cells induced to bm12 allografts in CCR5-deficient recipients were reactive to peptides spanning the 3 aa difference in the I-Abm12versus I-Ab b-chains presented by Kb and Db class I MHC molecules. Allograft-primed CD8 T cells from CCR5-deficient allograft recipients were activated during culture either with proinflammatory cytokine-stimulated wild-type endothelial cells pulsed with the I-Abm12peptides or with proinflammatory cytokine-simulated bm12endothelial cells, indicating their presentation of the I-Abm12b-chain peptide/class I MHC complexes. In addition to induction by bm12renal allografts, the I-Abm12b-chain-reactive CD8 T cells were induced in CCR5-deficient, but not wild-type C57BL/6, mice by immunization with the peptides. These results reveal novel alloreactive CD8 T cell specificities in CCR5-deficient recipients of single class II MHC renal allografts that mediate rejection of the allografts.
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