Relationship between Lymphokine and Opiatergic Modulation of Lymphocyte Proliferation

Abstract

T lymphocytes are primary effector cells of cell-mediated immunity as well as regulators of growth (clonal expansion) and differentiation of the immune system. Until less than a decade ago, their regulatory activity was presumed to be attributed to predominantly cellular interactions mediated by membrane-bound recognitive elements often associated with the major histocompatibility (H2 or HLA) complex. Recently, in the historical context of the development of immunological models, many regulatory functions of T lymphocytes appear to be mediated by molecules secreted by various functionally distinct subpopulations of lymphoid and nonlymphoid cells. Indeed, the principle regulatory cells of the immune system, T lymphocytes, are also under the regulatory influence of specific monocyte/ macrophage derived cytokines referred to as monokines. In addition to regulating lymphocyte activities, there is considerable evidence that lymphocyte-derived molecules, lymphokines, influence the differentiation of hematopoietic cells, mast cells, fibroblasts, and osteoclasts^1–6. This suggests that the regulatory cytokines produced by specific antigen may also effect hematopoietic homeostasis as well as inflammatory cells involved in immediate hypersensitivities. Lymphokines are considered to be actively synthesized (transcription of DNA) and secreted by either native lymphoid cells or their malignant cell line counterparts (macrophage or lymphocyte). While normal lymphoid tissues or cells must be activated by antigen or polyclonal stimulation to produce lymphokines, some longterm cell lines have been fortuitously shown to constitutively secrete lymphokines. Indeed, such cell lines have been critical for providing the genetic library for the recombinant DNA cloning of several lymphokines. Lymphokines provide nonspecific augmentation to antigen-specific responses. Lymphokines can generally be readily separated by conventional biochemical chromatography, but standard 280 nm absorbance and protein stains have been of little value since they are usually present in culture media in nanomolar concentrations. Finally, with the introduction of monoclonal antibodies, several lymphokines may be neutralized and quantitated in vitro by specific antibody.