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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 Systema

Authors

  • K. BULLOCH,

    Corresponding author
    1. Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York 10021 USA
      Address for correspondence: Dr. Karen Bulloch, Laboratory of Neuroendocrinology, The Rockefeller University-Box 165, 1230 York Ave., New York, NY 10021; Fax: 212-327-8634; e-mail: bullock@rockvax.rockefeller.edu
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  • B. S. McEWEN,

    1. Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York 10021 USA
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  • J. NORDBERG,

    1. Departments of Psychology and Pathology, University of California at San Diego, San Diego, California 92093 USA
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  • A. DIWA,

    1. Departments of Psychology and Pathology, University of California at San Diego, San Diego, California 92093 USA
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  • S. BAIRD

    1. Departments of Psychology and Pathology, University of California at San Diego, San Diego, California 92093 USA
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    This work was supported by National Institutes of Health supplement (3R37MH-41256-11 S1) and grant support to Rockefeller University from the Arthur Vining Davis Foundation.

Address for correspondence: Dr. Karen Bulloch, Laboratory of Neuroendocrinology, The Rockefeller University-Box 165, 1230 York Ave., New York, NY 10021; Fax: 212-327-8634; e-mail: bullock@rockvax.rockefeller.edu

Abstract

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 sparce 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.

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