title: Evaluation of immune regulation in transplant patients using the trans vivo delayed type hypersensitivity assay.
abstract: Allograft recipient IL-10 and/or transforming growth factor-beta (TGF-beta) dependent anti-inflammatory T-cell delayed type hypersensitivity (DTH) responses to donor derived antigens, or regulatory T-cell responses, have been demonstrated in rodents and transplant patients using a previously described trans vivo DTH assay. We used this assay to determine the incidence of recipient anti-inflammatory T-cell responses to donor antigens in a large cohort (n = 420) of primary kidney and simultaneous kidney-pancreas transplant patients tested a mean of 4.8 years after transplantation. The results were compared with clinical outcomes and the presence of detectable circulating alloantibodies. We found an unexpectedly high incidence (21.9%) of this anti-inflammatory T-cell response to donor antigens in these recipients. There was a significant correlation between this T-cell phenotype and the presence of detectable circulating alloantibodies (p = 0.03). There was no correlation between this T-cell phenotype and the degree of HLA mismatch. In addition, the presence of an anti-inflammatory DTH response to donor antigens did not correlate with an improved clinical outcome at a median of nearly 5 years after transplantation. These findings suggest that detection of an anti-inflammatory T-cell response to donor antigens does not identify patients that have developed graft protective, regulatory T-cell responses.
authors.affiliation: Department of General Surgery, The Ohio State University College of Medicine and Public Health, Columbus, OH, USA. ronald.pelletier@osumc.edu
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Pelletier
authors.forename: Alice A
authors.initials: AA
authors.lastname: Bickerstaff
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Adams
authors.forename: Charles G
authors.initials: CG
authors.lastname: Orosz
mesh_terms: D000328:Adult; D000368:Aged; D000941:Antigens / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000453:epidemiology* / Q000209:etiology; D007108:Immune Tolerance / Q000276:immunology*; D007118:Immunoassay / Q000379:methods; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation / Q000009:adverse effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014019:Tissue Donors
chemical_list: D000941:Antigens