CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones.
Occupancy of the T-cell antigen receptor is insufficient to induce T-cell activation optimally; a second co-stimulatory signal is required. Exposure of T-cell clones to complexes of antigen with major histocompatibility complex molecules in the absence of the co-stimulatory signal induces a state of clonal anergy. This requirement for two stimuli for T-cell activation could have an important role in vivo in establishing peripheral tolerance to antigens not encountered in the thymus. The receptor on T cells required for the co-stimulatory stimulus involved in the prevention of anergy has not been identified. The human T-cell antigen CD28 provides a signal that can synergize with T-cell antigen receptor stimulation in activating T cells to proliferate and secrete lymphokines. Here we report that a monoclonal antibody against the murine homologue of CD28 (ref. 7; J.A.G. et al., manuscript in preparation) can provide a co-stimulatory signal to naive CD4+ T cells and to T-cell clones. Moreover, we demonstrate that this co-stimulatory signal can block the induction of anergy in T-cell clones.
Harding
F A
FA
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
McArthur
J G
JG
Gross
J A
JA
Raulet
D H
DH
Allison
J P
JP
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D018106:CD28 Antigens; D015704:CD4 Antigens / Q000276:immunology; D002478:Cells, Cultured; D004261:DNA Replication; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000528:radiation effects; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D015704:CD4 Antigens