Reversibility with interleukin-2 suggests that T cell anergy contributes to donor-specific hyporesponsiveness in renal transplant patients.
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.
Ng
Wan Fai
WF
Department of Immunology, Hammersmith Hospital, Imperial College Faculty of Medicine, Du Cane Road, London W12 0NN, United Kingdom.
Hernandez-Fuentes
Maria
M
Baker
Richard
R
Chaudhry
Afzal
A
Lechler
Robert I
RI
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
D007376:Interleukin-2; D007518:Isoantibodies