Alloproliferative T4+ T8- Human T Cell Clones with Suppressive, Not Helper, Function

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The existence of at least three distinct subsets of human MHC class II molecules encoded by discrete genetic loci has been clearly established, namely HLA-DR, DQ, and DP. Products of each of these loci have been shown to function as alloantigens and as restriction elements in lymphoproliferative (LP) responses of T cells to allogeneic cells and to nominal antigens. However, it remains to be determined whether T cells reactive to the different subsets of class II molecules are endowed with different functional activities, since it cannot be assumed that proliferating lymphocytes are necessarily “helper” cells. Thus, the immunoregulatory activities of alloproliferative (primed lymphocyte typing, PLT) clones on lymphoproliferative (LP) responses were studied. The clones were derived as described [1] by limitation of dilution and expansion of clonal progeny in interleukin 2 (IL 2) from lymphocyte populations sensitized in (1) primary mixed lymphocyte cultures (MLCs) between HLA-D-mismatched donors: the majority of PLT clones (>60% in several priming combinations) recognized lymphocyte-activating determinants (LADs) closely associated with HLA-D region products [1]; (2) tertiary MLCs between HLA-D-matched, DP-mismatched donors: the majority (>90%) recognised LADs closely associated with DP products [2]; and (3) primary MLCs between HLA-D-matched, DP- mismatched donors: the majority (>70%), on the basis of population studies and stimulation inhibition with monoclonal antibodies against different class II molecules [3], recognised LADs similar to, but different from, alleles of the DP series, which have therefore been termed “DP-like” [4] and may represent the products of a second DP-related locus (1).