Figure 3. Effects of VIP/PACAP on Th cell differentiation. Although recent reports indicate that VIP affects dendritic cell (DC) maturation and migration (Delneste et al., 1999; Dunzendorfer et al., 2001), the effects of VIP and PACAP on dendritic cell (DC)–resting Th cell interactions remain to be investigated. VIP/PACAP inhibit IL-2 production and T-cell proliferation following initial exposure to the antigen. VIP/PACAP affect differentiation into effector Th cells, inhibiting Th1 and promoting Th2 differentiation. This effect is exerted through at least two separate pathways: (a) inhibition of IL-12 production (a required Th1 differentiation factor); and (b) posibly, through the up-regulation of macrophage B7.2, but not B7.1, by VIP/PACAP. Generation of memory Th cells requires survival of a small number of activated effectors following apoptosis, which eliminates most effectors at the end of the immune response. VIP/PACAP promote the survival of Th2, but not Th1, effectors, and the generation of long-term memory Th2 cells.