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.