Pretransplant frequency of donor-specific, IFN-gamma-producing lymphocytesis a manifestation of immunologic memory and correlates with the risk of posttransplant rejection episodes

While matching for MHC Ags improves renal allograft survival, closely match ed grafts sometimes fail due to rejection, and poorly matched allografts ar e often well tolerated by the recipient. The severity of the rejection proc ess may partially depend on the presence of environmentally primed T cells in the recipient that cross-react with donor Ags, To test for the presence of primed, donor-specific T cells in humans before transplantation, we used an enzyme-linked immunospot assay for detection of allospecific cytokines produced by individual human PBLs, We demonstrate that this approach detect s cytokine production at single cell resolution and detects production of I FN-gamma only when there is defined immunologic priming, thus representing a measure of primed donor-specific immunity. Because the environmental Ag e xposure of the recipient is not a function of the HLA mismatch between dono r and potential recipient, the number of HLA mismatches may not correlate w ith the frequency of pretransplant, donor-specific IFN-gamma-producing PBLs , Studies of donor-specific IFN-gamma-producing lymphocytes in a cohort of patients being evaluated for renal transplantation corroborated this hypoth esis. Moreover, for recipients of both living and cadaver renal allografts, the pretransplant frequency of donor-specific memory cells correlated with the posttransplant risk of developing acute rejection episodes. This impro ved ability to define the strength of the allospecific immune response by e nzyme-linked immunospot assay may allow improved pairing of recipients with donors and identification of kidney allograft donor-recipient pairs at hig h risk for acute rejection, thus permitting targeted interventions aimed at prolonging graft survival.