Vasoactive intestinal peptide and pituitary adenylate cyclase‐activating polypeptide promote in vivo generation of memory Th2 cells

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Abstract
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.
Funding Information
  • Presbyterian Historical Society (AI 041786-03, AI 47325-01, PM98-0081)