Vasoactive intestinal peptide induces regulatory T cells during experimental autoimmune encephalomyelitis.

CD4(+)CD25(+) regulatory T cells (Treg) control the immune response to a variety of antigens, including self-antigens. Several models support the idea of the peripheral generation of CD4(+)CD25(+) Treg from CD4(+)CD25(-) T cells. Little is known about the endogenous factors and mechanisms controlling the peripheral expansion of CD4(+)CD25(+) Treg. In this study we report on the capacity of the vasoactive intestinal peptide (VIP), an immunosuppressive neuropeptide, to induce functional Treg in vivo during the development of experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis model. The administration of VIP to EAE mice results in the expansion of the CD4(+)CD25(+), Foxp3-expressing T cells in the periphery and the nervous system, which inhibit encephalitogenic T cell activation. In addition to the increase in the number of CD4(+)CD25(+) Treg, VIP induces more efficient suppressors on a per cell basis. The VIP-generated CD4(+)CD25(+) Treg transfer suppression and significantly ameliorate the progression of the disease.