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*
Department of Biological Sciences, Rutgers University, Newark, NJ 07102; and
Departamento Biologia Celular, Universidad Complutense, Madrid, Spain
Vasoactive intestinal peptide (VIP) and the pituitary adenylate
cyclase-activating polypeptide (PACAP), two structurally related
neuropeptides produced within the lymphoid microenvironment, modulate
several immunologic functions. We have recently demonstrated that VIP
and PACAP enhance the macrophage costimulatory activity for naive
CD4+ T cells exposed to allogeneic or anti-CD3 stimuli
through the differential regulation of the B7 costimulatory molecules.
In this study, we report on the role of VIP and PACAP on macrophage B7
expression and costimulatory function for Ag-primed CD4+ T
cells, and on the macrophage-induced regulation of Th1/Th2
differentiation in vitro and in vivo. VIP and PACAP up-regulate the
costimulatory activity of macrophages for Ag-primed CD4+ T
cells. VIP-/PACAP-treated macrophages gain the ability to induce
Th2-type cytokines such as IL-4 and IL-5 and reduce Th1-type cytokines
such as IFN-
and IL-2. In vivo administration of VIP or PACAP in
Ag-immunized mice reduce the numbers of IFN--secreting cells and
enhance the numbers of IL-4-secreting cells. One of the consequences of
the VIP-/PACAP-induced shift in cytokine profile is a change in the
Ag-specific Ig isotype, increasing IgG1 and decreasing IgG2a levels.
Finally, the preferential differentiation into Th2 effector cells after
Ag stimulation induced by VIP-/PACAP-treated macrophages is mediated
through the up-regulation of B7.2 expression.
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