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 cell cytokine secretion, I tested four neuropeptides (NPs): somatostatin, calcitonin gene-related peptide, neuropeptide Y, and substance P. Comparing neuropeptide-driven versus classical antigen-driven cytokine secretion from T helper cells Th0, Th1, and Th2 autoimmune-related T cell populations, I show that the tested NPs, in the absence of any additional factors, directly induce a marked secretion of cytokines [interleukin 2 (IL-2), interferon-gamma, IL-4, and IL-10) from T cells. Furthermore, NPs drive distinct Th1 and Th2 populations to a "forbidden" cytokine secretion: secretion of Th2 cytokines from a Th1 T cell line and vice versa. Such a phenomenon cannot be induced by classical antigenic stimulation. My study suggests that the nervous system, through NPs interacting with their specific T cell-expressed receptors, can lead to the secretion of both typical and atypical cytokines, to the breakdown of the commitment to a distinct Th phenotype, and a potentially altered function and destiny of T cells in vivo.
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
M
M
Levite
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009478:Neuropeptide Y / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology*; D010641:Phenotype; D013004:Somatostatin / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D009478:Neuropeptide Y; D009479:Neuropeptides; D013373:Substance P; D013004:Somatostatin; D015740:Calcitonin Gene-Related Peptide