Gillis Otten

β-adrenergic receptors on splenic lymphocytes from axotomized mice

Adrenergic receptors are present on lymphocytes but the extent to which their activation modulates lymphocyte function remains unclear. We studied beta-adrenergic receptors on mouse spleen lymphocytes using the antagonist 3H-dihydroalprenolol (3H-DHA) as a specific ligand. We report a significant increase in beta-receptor density in spleen lymphocytes from mice treated with 6-hydroxydopamine (6-OHDA) to destroy peripheral sympathetic nerve endings (axotomy). Mouse spleen lymphocytes were separated into T and B subpopulations on nylon wool columns or by panning. B cells from both control and axotomized mice were found to bear twice as many beta-receptors as T lymphocytes. Finally, using flow cytometry to identify cells labeled with goat anti-mouse immunoglobulin (lg), axotomized mouse spleen lymphocyte populations were shown to contain 25% fewer B cells than controls. This work demonstrates differences in beta-adrenergic receptor density on functionally distinct populations of lymphocytes. Furthermore, we show adaptive changes in receptor density on T and B lymphocytes following sympathetic denervation. Both of these observations serve to link the immune and sympathetic nervous system in a regulatory network.

Regulation of Activation of Cloned Murine T Cells

Although helper T lymphocytes (HTL) and cytolytic T lymphocytes (CTL) share a number of common features, several lines of evidence indicate that they are controlled by distinctive regulatory mechanisms. Specifically, we have found that cloned murine CTL, in addition to proliferating in response to IL-2, also have an IL-2-independent pathway for replication; however, an IL-2-independent pathway has not been identified in our cloned murine HTL. HTL which secrete IL-2 become unresponsive to antigen following exposure to IL-2 while CTL do not; the limb of the T cell activation pathway leading to an increase in intracellular calcium appears to be selectively affected in this unresponsive state. In CTL–HTL hybrids constructed using a drug-marked variant of a cloned murine CTL, secretion of the full array of lymphokines can be induced by stimulating the antigen receptor of either the CTL or HTL partner. However, only target cells bearing antigens with which the CTL partner reacts can be lysed by the CTL–HTL hybrid cells; target cells bearing antigens with which the HTL partner reacts cannot be lysed. These differences appear to reflect separate regulatory mechanisms that control the responses of functionally distinct T cell subsets.