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The ability of cells of the immune system, immunocytes, to receive signals from the nervous as well as the endocrine system is dependent on the cells' expression of receptors for neurotransmitters and neurohormones. The number of receptors, especially beta adrenergic receptors (BARs), varies with the functional subset of immunocytes. However, little is known about how receptor number may vary during the life span (stem cell to mature activated immunocyte) of a given cell type. In this study, we have addressed this question by examining the affinities (Kd's) and the changes in receptor number (Bmax) on (1) clones of T cells and macrophages, (2) fresh thymocytes and splenocytes before and after activation with Concanavalin A (Con A) and phorbol myristate acetate (PMA)/Ca2+ ionophore (A23187), and (3) the cloned human monocyte U937 and the murine thymic lymphoma cell BW5147, in the presence and absence of PMA and A23187 ionophore. Drug treatments of fresh and cloned immunocytes alter the number but not the affinity of beta-receptors. Con A increases the number of beta-adrenergic receptors per cell, whereas PMA/ionophore decreases it. Similar decreases in BAR number are induced by PMA on cell lines BW5147 and U937. These data indicate that changes in receptor number can be regulated with different states of cell maturation and function. Thus, the immunological status of a given cell can influence the expression of BARs, thereby modulating its ability to respond to signals from the nervous and endocrine systems.

The glial tissue in Planorbis ganglia surrounds and ensheaths the neurons. The majority of the glial processes are interwoven around the neuronal perikarya and their major axon branches. Glial cell processes form a layer between the blood and nerve perikarya, but this does not significantly interfere with the movements of many small molecules in and out of the tissue. Such movements can occur paracellularly, through the extracellular spaces, since there are no occluding junctions between the cells.

Calcitonin gene-related peptide has been identified by immunocytochemistry within the thymus of fetal through aged adult mice. Calcitonin gene-related peptide positive nerves are observed from embryonic day 17 throughout the lifespan of the mouse. A sparse cell population positive for CGRP is first observed during the late embryonic period at the corticomedullary boundary and the medulla, and it becomes more densely distributed in this region in the adult. In the thymus of the aged mouse the number of CGRP-positive cells diminishes. Pharmacologic studies demonstrated that fresh thymocytes display a receptor Kd for CGRP of 1.17 +/- 0.06 x 10(-10)M and a Bmax of 12.7 +/- 4.7 fmol/mg protein. Functional studies indicate that CGRP is a potent inhibitor of mitogen and antigen-stimulated proliferation of T cells and that it inhibits IL-2 production in cloned splenic T cells. Recent studies suggest that endogenous CGRP may serve as a natural inhibitor of inappropriate induction of mature, antigen-sensitive cells in the thymus as well as play a role in thymocyte education. These findings are discussed in terms of the distribution of CGRP cells and nerve terminals within the thymus and their relationship to positive and negative selection of the T-cell repertoire.

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