STEROIDS AS REGULATORS OF THE MAMMALIAN IMMUNE-RESPONSE

The mammalian immune system is multicellular in composition, and its p roper function requires careful control over complex developmental pat hways and many distinct types of effector responses, Numerous overlapp ing mechanisms of intercellular communication are needed to accomplish the tasks of proper regulation of the diverse cell types that constit ute this essential protective system, One mechanism occurs by direct c ell-to-cell contact through the interaction of membrane-associated mol ecules, Examples of this type of communication include the interaction that takes place between the antigen-specific T-cell receptor and the foreign peptides that are bound to major histocompatibility complex m olecules, as well as costimulatory molecule interactions with their sp ecific ligands expressed on antigen-presenting cells (e.g., CD28 and B 7-1 or B7-2). A second mechanism occurs through the production, secret ion, and activities of soluble mediators, collectively known as the cy tokines, The cytokines are represented by a large and diverse group of molecules that are produced by a wide variety of cell types, Unique s pecies of cytokines bind to specific membrane-associated receptors on target cells, inducing the activation of particular signal-transductio n pathways, These processes subsequently lead to the diversity of cyto kine-linked changes in cellular physiology, Some of the cytokines erec t their influences in vivo via endocrine routes, although it is far mo re common for intercellular communication via cytokines to occur micro environmentally via paracrine or autocrine pathways, The object of thi s review is to provide evidence supporting the concept that one mechan ism for upstream regulation of cytokine production by immunocompetent cell types is controlled by the regulatory activities of various stero id hormones, Strain variation in susceptibility to infectious agents, the condition of immunosenescence, and the processes that control the development of common mucosal immunity are used as examples of immune mechanisms that may be under steroid hormone control.