HLA-DR specific human suppressor lymphocytes generated by repeated in vitro sensitisation against allogeneic cells

Abstract

THE HLA complex is composed of a set of genes closely linked on chromosome 6, which may have important functions in the regulation of the immune response. The HLA-A, -B and -C loci control serologically defined antigens present on most cells. The HLA-D region controls two groups of determinants: (1) HLR-DR (DRwl to DRw8) antigens, restricted to B lymphocytes, detected by serology and equivalent to the I region-associated antigens (Ia) of the mouse; (2) HLA-D stimulating products (Dw1 to Dw11) defined by mixed lymphocyte reactions (MLR). Sensitisation of human lymphocytes with irradiated allogeneic stimulatory cells in vitro produces primed lymphocytes^1–5. These in vitro primed lymphocytes develop an accelerated secondary proliferative response when restimulated by the specific priming cell or by any cell possessing HLA-D region products identical to the priming cells. Familial and population studies^6,7 show this secondary proliferation (MLR II or PLT) to be more correlated to HLA-DR antigens serologically detected than to D specificites defined by HLA-D typing (MLR I). It has also been suggested that, within informative families bearing haplotypes with unusual associated D-DR products, DR antigens and HLA-D stimulating products could be distinct determinants⁷. However, absolute proof—a recombination between these two products—is still lacking. The accelerated proliferative capacity of primed lymphocytes represents a function which depends on the allogeneic contact; we have investigated the possible induction of suppresor cells by repeated in vitro sensitisation. We show that lymphocytes sensitised twice ‘in vitro’ behave as active suppressors of the allogeneic response and are specific for the HLA-DR antigens presented by the stimulator lymphocytes.