B7-1 AND B7-2 DO NOT DELIVER IDENTICAL COSTIMULATORY SIGNALS, SINCE B7-2 BUT NOT B7-1 PREFERENTIALLY COSTIMULATES THE INITIAL PRODUCTION OF IL-4

The functional necessity for two CD28 counterreceptors (B7-1 and B7-2) is presently unknown. B7-1 and B7-2 equivalently costimulate IL-2 and interferon-gamma (IFN gamma) production and IL-2 receptor alpha and gamma chain expression. B7-2 induces significantly more IL-4 production than B7-1, with the greatest difference seen in naive T cells. Repetitive costimulation of CD4(+) CD45RA(+) T cells with B7-2 results in moderate levels of both IL-4 and IL-2, whereas repetitive costimulation with B7-1 results in high levels of IL-2 and low levels of IL-4. Therefore, B7-1 and B7-2 costimulation mediate distinct outcomes, since B7-2 provides an initial signal to induce naive T cells to become IL-4 producers, thereby directing the immune response more towards Th0/Th2, whereas B7-1 is a more neutral differentiative signal.