Vasoactive intestinal peptide generates CD4+CD25+ regulatory T cells in vivo: therapeutic applications in autoimmunity and transplantation.
CD4+ CD25+ regulatory T cells (Treg) 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+ Treg 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+ Treg 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.
Chorny
Alejo
A
Instituto de Parasitologia y Biomedicina, CSIC, Avd. Conocimiento, PT Ciencias de la Salud, Granada 18100, Spain.
Gonzalez-Rey
Elena
E
Ganea
Doina
D
Delgado
Mario
M
D000818:Animals; D015551:Autoimmunity / Q000187:drug effects* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D017690:Cell Transplantation; D002478:Cells, Cultured; D051379:Mice; D008822:Mice, Transgenic; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D014660:Vasoactive Intestinal Peptide