Generation of CD4-positive suppressor T cells from mixed lymphocyte cultures in the presence of interleukin 2 receptor antibody TU69. An in vitro model for transplantation tolerance induction.
The specificity of a novel monoclonal antibody (moAB), TU69, directed to the interleukin 2 receptor (IL-2R) was verified by sequential immunoprecipitation with anti-Tac. TU69 cross-competed with anti-Tac in binding analyses. When TU69 was added during the sensitization of normal peripheral blood mononuclear cells (PBMC) to allogeneic HLA-class I or -class II mismatched stimulator PBMC, alloproliferative responses and specific cytotoxicity were no longer detectable and the generation of natural killer (NK)-like effector cells was partially inhibited. Remarkably, however, the generation of CD4+ nonspecific suppressor T cells in such mixed lymphocyte cultures (MLC) was not inhibited--but, in contrast, was strongly enhanced in the presence of TU69. These suppressor cells inhibited unrelated allospecific responses in vitro to background levels even at a ratio of 50:1 responder:irradiated suppressor T cell lines. Such a potent experimental suppressor system suggests a possible application of TU69 for in vivo tolerance induction after transplantation, by down-regulating allospecific effector cells and allowing the generation of tolerance to graft antigens.
D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000032:analysis*; D002999:Clone Cells / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D011971:Receptors, Immunologic / Q000276:immunology*; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2