Inhibition of the anti-CD3-induced T cell proliferation by crosslinking of stimulatory antibodies in the presence of PMA and interleukin-2.
Anti-CD3 antibodies are directed to the nonpolymorphic part of the T cell receptor complex and may activate human peripheral T cells. Under some circumstances crosslinked anti-CD3 has been described to augment the proliferative response. Here we demonstrate that crosslinking of stimulatory anti-CD3 antibodies by anti-IgG in cell suspension abolishes their effect on proliferation of human resting peripheral T cells in the presence of PMA and/or IL-2. This effect was observed within a wide range of anti-CD3 concentrations (1 ng/ml to 1 microgram/ml) independent of the presence of monocytes. The inhibition was not due to the induction of cell death, since cells remained propidium iodide-negative after treatment. Protein-tyrosine phosphorylation after anti-CD3 crosslinking was more pronounced than in the presence of noncrosslinked anti-CD3. This indicates that the signal was transmitted after anti-CD3 crosslinking, however, it was unable to induce T cell proliferation. Reduced IL-2 receptor expression after anti-CD3 crosslinking and the inability of exogenous IL-2 to restore the proliferative response might indicate a reduced susceptibility to IL-2 as a reason for the described phenomenon.
Tsygankov AYu
Max-Planck-Society, Research Unit for Rheumatology/Immunology, Erlangen, Federal Republic of Germany.
Bröker
B M
BM
Emmrich
F
F
D016923:Cell Death; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology*; D009000:Monocytes / Q000276:immunology; D016853:Muromonab-CD3 / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007140:Immunoglobulin Fab Fragments; D007376:Interleukin-2; D016853:Muromonab-CD3; D015375:Receptors, Interleukin-2; D011505:Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate