Monocytes provide a novel costimulatory signal to T cells that is not mediated by the CD28/B7 interaction.
Resting CD4+T cells must receive nonspecific costimulatory signals from APC to produce maximal amounts of IL-2 in response to TCR signaling. The T cell-specific surface molecule CD28 is one protein that transduces a costimulatory signal following interaction with its ligand B7. We report here the identification of another contact-mediated costimulatory signal provided by the human histiocytic line U937 and by purified monocytes. Although this monocyte-derived costimulus is not transduced by the CD28/B7 interaction, it synergizes with the CD28 signal to elicit maximal IL-2 production from freshly isolated T cells. IL-2 production by previously activated CD8+ T cells depends on the monocyte-derived costimulatory signal, although memory CD4+ T cells respond well to either the monocyte-derived costimulus or B7-derived costimulation. In contrast, IL-2 secretion by naive T cells appears to require the synergistic interaction between both costimulatory pathways. These results suggest that the array of costimulatory ligands expressed by various APC affects the magnitude of the T cell response and also which T cell subsets are stimulated.
Johnson
J G
JG
Department of Microbiology, University of Minnesota Medical School, Minneapolis 55455.
Jenkins
M K
MK
D018122:B7-1 Antigen / Q000502:physiology*; D018106:CD28 Antigens / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014407:Tumor Cells, Cultured
D018122:B7-1 Antigen; D018106:CD28 Antigens; D016827:CD8 Antigens; D017493:Leukocyte Common Antigens