Inhibition of antigen-specific proliferation of type 1 murine T cell clones after stimulation with immobilized anti-CD3 monoclonal antibody.
The effect of stimulating normal type 1 murine T cell clones with anti-CD3 antibody was examined in vitro. In the absence of accessory cells, anti-CD3 antibody immobilized on plastic plates stimulated inositol phosphate production, suboptimal proliferation, IL-2 and IL-3 production, and maximal IFN-gamma production. Addition of accessory cells augmented lymphokine production and proliferation when the effects of "high-dose suppression" were relieved by removing the T cells from the antibody-coated plates. Exposure of type 1 T cell clones to immobilized anti-CD3 antibody alone rapidly induced long-lasting proliferative unresponsiveness (anergy) to Ag stimulation that could be prevented by accessory cells. This anergic state was characterized by a lymphokine production defect, not a failure of the T cells to respond to exogenous IL-2 or to express surface Ti/CD3 complexes. In addition, anergy could not be induced in the presence of cyclosporine A. These results suggest that under certain conditions anti-CD3 antibodies may have potent immunosuppressive effects independent of Ti/CD3 modulation. Furthermore, our results support a two-signal model of type 1 T cell activation in which Ti/CD3 occupancy alone (signal 1) induces anergy, whereas Ti/CD3 occupancy in conjunction with a costimulatory signal (signal 2) induces a proliferative response.
Jenkins
M K
MK
Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Chen
C A
CA
Jung
G
G
Mueller
D L
DL
Schwartz
R H
RH
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D017252:CD3 Complex; D003524:Cyclosporins / Q000494:pharmacology; D003574:Cytochrome c Group / Q000276:immunology; D007108:Immune Tolerance; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D007518:Isoantibodies / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000096:biosynthesis; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000502:physiology*; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D003524:Cyclosporins; D003574:Cytochrome c Group; D007295:Inositol Phosphates; D007518:Isoantibodies; D008222:Lymphokines; D011948:Receptors, Antigen, T-Cell