CLUES TO IMMUNE FUNCTION AND ONCOGENESIS PROVIDED BY EVENTS THAT ACTIVATE THE CELL-CYCLE MACHINERY IN NORMAL HUMAN T-CELLS

A common feature seen in states of decreased immune competence or immu nosuppression and in diseases of the blood, such as lymphohematopoieti c cancers, is the disruption of the normal pathways of cell cycle cont rol. In lymphocytes a series of nonlinear biochemical cascades leads t o cellular proliferation and also controls the production of cytokines that provide immunologic help (i.e., aid in B and T cell proliferatio n, maturation, and differentiation). These two distinct outcomes can b e dissociated, as stimuli that incite production of cytokines need not lead to cell division, and conversely, exogenously provided cytokines may promote lymphocyte proliferation. The signals that induce product ion of cytokines, particularly interleukin-2, have been extensively ch aracterized. It also is known that the fidelity of cell cycle progress ion is dependent on a regulatory network whose key components include cyclin-dependent kinases and cyclins. This review describes the curren t state of knowledge linking the antigen receptor response pathways an d the activation of the cell cycle machinery in T cells.