Persistence of dominant T cell clones in accepted solid organ transplants

Donor/recipient MHC class II matching is beneficial to the survival of allo geneic kidneys in humans and swine. In the latter, tolerance to class I-dis parate grafts can be induced by a short course of immunosuppression, a peri pheral mechanism that implicates regulatory T cells. Absence of treatment w ill lead to prompt rejection. Rejected grafts are infiltrated by dominant a lloaggressive T cells, whereas there is still speculation on the specificit y and function of T cells invading accepted tissues. To characterize the TC R repertoire of graft-infiltrating T cells (GITC) in accepted kidneys, we h ave used the RT-PCR-based spectratyping technique to assess the length poly morphism of the porcine TCR beta chain complementary-determining region 3 ( CDR3). Results show that T cells infiltrating accepted kidneys (n = 5) expr ess a restricted polymorphism of the CDR3 length, whereas PBL from the same animal have the polymorphic distribution of CDR3 lengths found in naive an imals; that the skewed V beta repertoire in accepted grafts involved distin ct V beta subfamilies in otherwise MHC-identical recipient animals; that GI TC clonal dominance is not caused by immunosuppression because a second kid ney, accepted without drug treatment, exhibits the same TCR V beta CDR3 pro files than those detected in the first graft; and that intragraft clonal do minance intensifies with time, indicating progressive preeminence of nonagg ressive GITC clones. Collectively, these data represent the first example, in a preclinical model, of the emergence of nonaggressive intragraft clones , which may be involved in the induction/maintenance of local tolerance to allogeneic tissues.