Human T lymphocyte activation by monoclonal antibodies; OKT3, but not UCHT1, triggers mitogenesis via an interleukin 2-dependent mechanism.
OKT3 and UCHT1 monoclonal antibodies, which recognize the same human T cell surface antigen, induce proliferation in T lymphocytes. In this report, we compared the mechanism by which these antibodies trigger DNA synthesis in human peripheral blood mononuclear cell (PBMC) cultures. Whereas PBMC from all donors tested were mitogenically inducible by OKT3, cells from only 25 of 40 donors were responsive to UCHT1 . UCHT1 treatment of PBMC from responders, but not from nonresponders, resulted in the expression by T cells of membrane binding sites reactive with anti-Tac monoclonal antibody, which specifies the human interleukin 2 (IL 2) receptor. UCHT1 -induced PBMC supernatants from nonresponders, but unexpectedly, also from responders, contained no measurable IL 2 activity. In keeping with this finding, anti-Tac monoclonal antibody failed to suppress UCHT1 -triggered [3H]thymidine incorporation into PBMC from responsive donors. By contrast, OKT3 treatment of PBMC from all donors led to the emergence of IL 2 receptors, and substantial IL 2 production, and the resultant DNA synthesis was inhibitable by anti-Tac antibody. These data indicate that the interaction of OKT3 and UCHT1 monoclonal antibodies with the same T cell structure leads to the induction of proliferation via two different mechanisms: one dependent on the availability of IL 2 (OKT3) and one independent on the production and processing of this lymphokine ( UCHT1 ). PBMC unresponsiveness to UCHT1 could therefore not be related to a dysfunction in IL 2 synthesis or IL 2 receptor display.
D000328:Adult; D000911:Antibodies, Monoclonal / Q000502:physiology*; D000954:Antigens, Surface / Q000276:immunology; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000378:metabolism / Q000502:physiology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000276:immunology / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000096:biosynthesis; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007376:Interleukin-2; D008934:Mitogens; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7