Control of Immune Responses by Cyclic Amp and Lymphocytes that Adhere to Histamine Columns

Abstract

Mixed lymphocytes from human peripheral blood, murine spleens, lymph nodes or thymus glands have pharmacologically specific receptors for histamine, beta mimetic catecholamines and prostaglandins. When these cells are exposed to the panoply of drugs mentioned above, their intracellular cyclic AMP concentrations increase. The biologic consequences of such an increase were at first elusive. Now we know that the immune potential of some murine spleen cells may be modulated and the release of lysosomal enzymes and histamine from human leukocytes may be inhibited. This paper concentrates on the effects that manipulation of cells with amine receptors has on their immune function. Recent studies have revealed that a subpopulation of splenic suppressor T cells responds to increases in its cyclic AMP content by reversing its suppressive effects on the humoral antibody response. When these T cells are removed from the murine cell population by their differential adherence to insolubilized conjugates of histamine with albumin, the remainder of the cells are more responsive to sheep cell antigen, as tested by transferring the spleen cells together with the antigen into lethally irradiated recipient animals. The suppressor T cells that adhere to the insolubilized conjugates of histamine-albumin (called histamine-rabbit serum albumin-Sepharose, or HRS) are Ia positive, they appear to have receptors for histamine, beta adrenergic amines and prostaglandins of the E series, and when stimulated by these agents their in vivo and in vitro suppressor actions are reversed. The reversal seems quantitatively dependent on cyclic AMP accumulation. Receptors for the amines and prostaglandins are found on the T cell precursors of cell mediated immunity. They develop on some T effector cells in selected models of allogeneic target cell lysis. The receptors also appear to develop on selected B cells once these cells become committed to antibody production. The distribution of receptors on all leukocytes has not been adequately studied nor has their full potential in the immune response been studied in detail.