The role of calcitonin gene-related peptide in the mouse thymus revisited.

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.

Changes in beta-adrenergic receptor distribution on immunocytes during differentiation: an analysis of T cells and macrophages.

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.

Calcitonin gene-related peptide in the developing and aging thymus. An immunocytochemical study.

Calcitonin gene-related peptide (CGRP) is known to block Con A and PHA induced T cell proliferation. As a first step in determining the role of this peptide in T cell education and function we have studied the distribution of CGRP within the developing mouse thymus using immunocytochemistry. CGRP-like immunoreactivity (CGRP-IR) was found in the thymic nerves in close proximity to blood vessels in the 17-day-old embryonic mouse thymus. A discrete population of small cells at the cortico-medullary junction also stained intensely for CGRP. As the mouse thymus reached maturity (three to eight weeks) CGRP innervation became more dense, with fibers running along the vasculature at the cortico-medullary boundary, then branching into the cortical and medullary regions. Some fibers were invested in the blood vessels while a large portion formed varicosities among the cells of the thymus. In the mature thymus, the small CGRP-IR cortico-medullary cells were more numerous, and CGRP-IR was also found in subcapsular and trabecular mast cells. The pattern of innervation remained the same in the aging mouse thymus (six months), but there appeared to be somewhat fewer cortico-medullary cells and an increase in mast cell number. In the aged (eighteen months) thymus, the small CGRP-IR cortico-medullary cells were rarely seen, but mast cells were more numerous, most of which stained positively for CGRP, in the connective tissue. Nerves containing CGRP-IR generally had the same distribution as in the younger mice but appeared somewhat truncated. The distribution of CGRP-IR nerves in the mouse thymus at different stages of development was similar to that reported for cholinergic (AChE-positive) nerves. Since the brain-stem vagal nuclei have been shown by retrograde transport studies to project to the thymus as well as to contain CGRP-IR neurons, our findings suggest that CGRP-IR thymic nerves may be derived from the vagus complex.

Quantitative analysis of neuron-glial relationships in the buccal ganglion of Planorbis: life constancy in the absence of changes in functional output.

The numbers and volumes of the neurons and glial cells in the buccal ganglia of Planorbis were analyzed by a new technique (computer image analysis of serial-section autoradiograms). The nerve-glia relationship are remarkably constant in the ganglia throughout the adult life of the animal (4-5 years), which correlates with their unchanging functional output to control the feeding cycle of the animal.