Induction of interleukin 2 receptiveness and proliferation in resting peripheral T cells by monoclonal anti-CD3 (T3) antibodies does not require the presence of macrophages.
In this study, we sought to elucidate the sequence of events by which mitogenic monoclonal anti-CD3 antibodies (anti-CD3-MoAb) initiate T cell activation. In cultures of monocyte-depleted resting T cells, two anti-CD3-MoAb, OKT3 and anti-Leu 4, induced a state of interleukin 2 (IL-2) receptiveness which culminated in T lymphocyte proliferation when recombinant IL-2 was provided. Evidence that Fc-receptor mediation by monocytes did not contribute to this mitogenesis was supported by studies showing that polyclonal F(ab')2 anti-mouse IgG Fc antibody did not alter the magnitude of the IL-2 driven T cell proliferative response, and by the use of T cells from donors whose monocytes were unable to assist in the induction of anti-Leu 4 (IgG1 subclass) initiated proliferation. Anti-CD3-MoAb, in the absence of IL-2, induced IL-2 receptor expression on purified T cells, and anti-IL 2 receptor antibodies inhibited T cell proliferation in the presence of this growth factor. Furthermore, following modulation of the CD3 molecular complex in the presence of monocytes, depletion of accessory cells rendered the modulated T cells mitogenically dependent on exogenous IL-2. IL-2 itself did not suffice to promote T cell proliferation in the absence of anti-CD3-MoAb. These results indicate that the binding of monoclonal antibody to CD3 is capable of initiating, in an accessory cell-independent manner, premitotic alterations in T cells which can culminate in proliferation when exogenous IL-2 is provided.
D000911:Antibodies, Monoclonal / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology*; D008938:Mitosis; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2