title: Selective regulation of T-cell development and function by calcitonin gene-related peptide in thymus and spleen. An example of differential regional regulation of immunity by the neuroendocrine system.
abstract: In the course of our studies, we have shown the presence of calcitonin gene related peptide (CGRP) by immunocytochemistry in cell bodies and nerve fibers of the murine thymus and in a sparse innervation of the spleen. Receptors for CGRP have been characterized within these glands, and their activation by physiological levels of CGRP was found to suppress Con A-stimulated proliferation of thymocytes and splenic T cells as well as antigen-specific T-cell proliferation. This suppression is blocked by the antagonist for CGRP (CGRP 8-37). Within the thymus cultures, the antagonist CGRP (8-37) alone enhanced proliferation of thymocytes during Con A stimulation, most likely by inhibiting the endogenous release of CGRP into the culture medium by resident thymocytes. Some of the CGRP-induced suppression of mitogenic stimulation of thymocytes, but not of splenocytes, was due to apoptosis. The antagonist, CGRP(8-37), did not block apoptosis caused by Con A or CGRP but rather enhanced it. Flow cytometric analysis of CGRP-treated cultures using antibodies to cluster determinates (CD) showed that the majority of thymocytes undergoing apoptosis induced by CGRP were of the CD4/CD8 double-positive type. These data indicate that apoptosis in the thymocytes is mediated by a CGRP receptor not sensitive to the antagonist CGRP(8-37). Because proliferation of thymocytes and splenocytes induced by Con A is blocked by this antagonist and splenocytes are refractory to CGRP induced apoptosis, CGRP appears to mediate at least two separate functions on subpopulations of thymocytes and T cells via two different CGRP receptors within the gland. These effects of a neuropeptide exemplify the phenomenon of differential regional regulation of immunity by the autonomic and neuroendocrine systems.
authors.affiliation: Laboratory of Neuroendocrinology, Rokefeller University, New York, NY 10021, USA. bullock@rockvax.rockefeller.edu
authors.forename: K
authors.initials: K
authors.lastname: Bulloch
authors.forename: B S
authors.initials: BS
authors.lastname: McEwen
authors.forename: J
authors.initials: J
authors.lastname: Nordberg
authors.forename: A
authors.initials: A
authors.lastname: Diwa
authors.forename: S
authors.initials: S
authors.lastname: Baird
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D017209:Apoptosis; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D007109:Immunity / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009490:Neurosecretory Systems / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D015740:Calcitonin Gene-Related Peptide