NEUROPEPTIDES, BY DIRECT INTERACTION WITH T-CELLS, INDUCE CYTOKINE SECRETION AND BREAK THE COMMITMENT TO A DISTINCT T-HELPER PHENOTYPE

Searching for nervous system candidates that could directly induce T c ell cytokine secretion, I tested four neuropeptides (NPs): somatostati n, calcitonin gene-related peptide, neuropeptide Y, and substance P. C omparing neuropeptide-driven versus classical antigen driven cytokine secretion from T helper cells Th0, Th1, and Th2 autoimmune-related T c ell populations, I show that the tested NPs, in the absence of any add itional factors, directly induce a marked secretion of cytokines [inte rleukin 2 (IL-2), interferon-gamma, IL-4, and IL-10) from T cells. Fur thermore, NPs drive distinct Th1 and Th2 populations to a ''forbidden' ' cytokine secretion: secretion of Th2 cytokines from a Th1 T cell lin e and vice versa. Such a phenomenon cannot be induced by classical ant igenic stimulation. My study suggests that the nervous system, through NPs interacting with their specific T cell-expressed receptors, can l ead to the secretion of both typical and atypical cytokines, to the br eakdown of the commitment to a distinct Th phenotype, and a potentiall y altered function and destiny of T cells in vitro.