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

While matching for MHC Ags improves renal allograft survival, closely matched grafts sometimes fail due to rejection, and poorly matched allografts are often well tolerated by the recipient. The severity of the rejection process 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 detects cytokine production at single cell resolution and detects production of IFN-gamma only when there is defined immunologic priming, thus representing a measure of primed donor-specific immunity. Because the environmental Ag exposure of the recipient is not a function of the HLA mismatch between donor and potential recipient, the number of HLA mismatches may not correlate with 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 hypothesis. 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 improved ability to define the strength of the allospecific immune response by enzyme-linked immunospot assay may allow improved pairing of recipients with donors and identification of kidney allograft donor-recipient pairs at high risk for acute rejection, thus permitting targeted interventions aimed at prolonging graft survival.

A monoclonal antibody detecting a possible public specificity of the HLA-C locus.

An IgM monoclonal antibody (CC-Cl 11) was produced by fusing myeloma cell line SP2/08 with lymphocytes of a Balb/c mouse previously immunized with peripheral blood lymphocytes of an A2, Bw44, B27, Cw1, Cw7, DR5 donor. Reactivity of CC-Cl 11 on a lymphocyte panel of 172 unrelated donors and lysostripping and absorption experiments have shown that CC-Cl 11 recognizes an antigenic determinant common to HLA-Cw1 and Cw3 positive lymphocytes.

Study of HLA antigens in familial and sporadic rheumatoid arthritis.

Patients with familial and non-familial (sporadic) forms of rheumatoid arthritis (RA) were studied to investigate possible HLA heterogeneity. HLA-DR4 was present in 75% of familial and 59% of sporadic RA patients. The frequency distribution of A2, B8, B27, Cw3 and DR3 differed somewhat between the two groups; however, the differences were not statistically significant in this small group of patients. Studies of a larger number of patients are indicated to explore the possibility of genetic subgroups in RA.