title: Reversibility with interleukin-2 suggests that T cell anergy contributes to donor-specific hyporesponsiveness in renal transplant patients.
abstract: Data from various rodent models have implicated a role for anergic T cells in the maintenance of self and transplantation tolerance. The relevance of donor-specific T cell anergy to clinical transplantation, however, has not been demonstrated. Previous studies have reported that recipients of solid organ transplant often have reduced frequencies of CD4(+) T cells with anti-donor direct pathway allospecificity after transplantation. The underlying mechanism(s) of this donor-specific hyporesponsiveness is unclear but likely to contribute to the diminished immunosuppressive requirement of transplant patients with time after transplantation. This study shows that ex vivo treatment of CD4(+) T cells from renal transplant recipients with IL-2 could specifically increase the anti-donor frequency in all the patients with evidence of donor-specific hyporesponsiveness. It also shows that the IL-2-induced recovery of anti-donor frequency is unlikely to result from nonspecific stimulation or selective clonal expansion of activated, allospecific CD4(+) T cells. Taken together, the data suggest that T cell anergy plays an important role in the direct pathway hyporesponsiveness that evolves in many human renal transplant recipients.
authors.affiliation: Department of Immunology, Hammersmith Hospital, Imperial College Faculty of Medicine, Du Cane Road, London W12 0NN, United Kingdom.
authors.forename: Wan Fai
authors.initials: WF
authors.lastname: Ng
authors.forename: Maria
authors.initials: M
authors.lastname: Hernandez-Fuentes
authors.forename: Richard
authors.initials: R
authors.lastname: Baker
authors.forename: Afzal
authors.initials: A
authors.lastname: Chaudhry
authors.forename: Robert I
authors.initials: RI
authors.lastname: Lechler
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007518:Isoantibodies / Q000032:analysis; D016030:Kidney Transplantation / Q000276:immunology*; D008875:Middle Aged; D012016:Reference Values; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology*; D014019:Tissue Donors
chemical_list: D007376:Interleukin-2; D007518:Isoantibodies