Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide promote in vivo generation of memory Th2 cells.
Functionally active effector T cells are generated through clonal expansion. Most effector T cells are later eliminated, whereas a small number survive and differentiate into memory T cells. The mechanisms by which some effector T cells escape apoptosis and become memory T cells are not understood. Neuropeptides such as the vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) inhibit antigen-induced apoptosis of CD4 T cells. By using an in vivo long-term experimental model, in which CD4 T cells from TRC-transgenic mice were transferred into hosts, we demonstrate that VIP and PACAP induce the survival and/or generation of antigen-specific CD4 T cells with a memory Th2 phenotype. This was confirmed by the fact that transgenic CD4 T cells were recovered only from mice that received Th2, but not Th1 effector cells, in the presence of VIP or PACAP. In vitro, VIP/PACAP support the survival of Th2, but not Th1, cell lines through an inhibition of antigen-induced apoptosis. The role of neuropeptides in the biased development of Th2 memory cells is particularly relevant in view of the immune deviation existing in immune-privileged sites such as the brain and eye, where Th2, but not Th1, responses occur in nonpathological conditions.
Delgado
Mario
M
Department of Biological Sciences, Rutgers University, Newark, New Jersey, USA. mariodm@bio.ucm.es
Leceta
Javier
J
Ganea
Doina
D
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D007156:Immunologic Memory; D051379:Mice; D009479:Neuropeptides / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
C495402:Adcyap1 protein, mouse; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide