Persistence of dominant T cell clones in accepted solid organ transplants.
Donor/recipient MHC class II matching is beneficial to the survival of allogeneic kidneys in humans and swine. In the latter, tolerance to class I-disparate grafts can be induced by a short course of immunosuppression, a peripheral mechanism that implicates regulatory T cells. Absence of treatment will lead to prompt rejection. Rejected grafts are infiltrated by dominant alloaggressive T cells, whereas there is still speculation on the specificity and function of T cells invading accepted tissues. To characterize the TCR repertoire of graft-infiltrating T cells (GITC) in accepted kidneys, we have used the RT-PCR-based spectratyping technique to assess the length polymorphism of the porcine TCRbeta chain complementary-determining region 3 (CDR3). Results show that T cells infiltrating accepted kidneys (n = 5) express a restricted polymorphism of the CDR3 length, whereas PBL from the same animal have the polymorphic distribution of CDR3 lengths found in naive animals; that the skewed Vbeta repertoire in accepted grafts involved distinct Vbeta subfamilies in otherwise MHC-identical recipient animals; that GITC clonal dominance is not caused by immunosuppression because a second kidney, accepted without drug treatment, exhibits the same TCR Vbeta CDR3 profiles than those detected in the first graft; and that intragraft clonal dominance intensifies with time, indicating progressive preeminence of nonaggressive 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.
Baron
C
C
Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
McMorrow
I
I
Sachs
D H
DH
LeGuern
C
C
D000818:Animals; D002999:Clone Cells; D022801:Complementarity Determining Regions / Q000235:genetics*; D017931:DNA Primers; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D019674:Genes, T-Cell Receptor beta; D006085:Graft Survival / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D011110:Polymorphism, Genetic; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology*
D022801:Complementarity Determining Regions; D017931:DNA Primers