title: Regulatory CD25+ T cells in human kidney transplant recipients.
abstract: Recent evidence suggests that a population of professional regulatory cells, which limit immune responsiveness, exist in rodents and healthy human subjects. However, their role in disease states remains unclear. A proportion of renal transplant recipients do not demonstrate in vitro reactivity toward their mismatched donor-derived HLA-DR antigens; it was therefore hypothesized that this may be due to such regulatory cells. A cohort of 23 renal transplant recipients was studied at a single institution. In patients with no history of acute rejection, 6 (40%) of 15 demonstrated regulation toward the mismatched HLA-DR allopeptides by CD25(+) cells. By contrast, only one (12.5%) in eight of those with a history of acute rejection demonstrated regulation. Interestingly, if the patient assays were stratified according to initial in vitro immune responsiveness toward the mismatched allopeptides, 8 (47.1%) of 17 of patient assays with low allopeptide responsiveness (alloreactive T cell frequencies less than 60/million) demonstrated regulation of indirect pathway alloresponses by CD25(+) cells, whereas 0 of 8 with higher responses (frequencies greater than 60/million) demonstrated no such regulation (P < 0.05 by chi(2) test). The regulatory cells are present in the circulation as early as 3 mo after transplantation and persist for a number of years, despite conventional immunosuppression. Furthermore, induction treatment with anti-IL-2R mAb did not prevent the development of these regulatory CD25(+) cells. Data from two patients suggest that these cells may also play a role in preventing epitope shifting, implicated in the ongoing immune activation contributing to chronic rejection, and that loss of regulation in a given patient may precede an episode of rejection.
authors.affiliation: Laboratory of Immunogenetics and Transplantation, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Salama
authors.forename: Nader
authors.initials: N
authors.lastname: Najafian
authors.forename: Michael R
authors.initials: MR
authors.lastname: Clarkson
authors.forename: William E
authors.initials: WE
authors.lastname: Harmon
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Sayegh
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007519:Isoantigens / Q000276:immunology; D016030:Kidney Transplantation; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000032:analysis* / Q000276:immunology; D014019:Tissue Donors
chemical_list: D000911:Antibodies, Monoclonal; D006684:HLA-DR Antigens; D007519:Isoantigens; D015375:Receptors, Interleukin-2