Vasoactive intestinal peptide generates CD4+CD25+ regulatory T cells in vivo -: Therapeutic applications in autoimmunity and transplantation

CD4(+) CD25(+) regulatory T cells (T-reg) control the immune response to a variety of antigens, including self-antigens, and several models support the idea of the peripheral generation of CD4(+) CD25(+) T-reg from CD4(+) CD25(-) T cells. However, little is known about the endogenous factors and mechanisms controlling the peripheral expansion of CD4(+) CD25(+) Treg, We have found that the immunosuppressive neuropeptide vasoactive intestinal peptide (VIP) induces functional Treg in vivo. The administration of VIP together with specific antigen to TCR-transgenic mice results in the expansion of the CD4+ CD25(+), Foxp-3/neuropilin 1-expressing T cells, which inhibit responder T cell proliferation through direct cellular contact. The VIP-generated CD4(+) CD25(+) T-reg transfer suppression, inhibiting delayed-type hypersensitivity in the hosts, prevent graft-versus-host disease in irradiated host reconstituted with allogeneic bone marrow, and significantly ameliorate the clinical score in the collagen-induced arthritis model for rheumatoid arthritis and in the experimental autoimmune encephalomyelitis model for multiple sclerosis.