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 immunosuppression and in diseases of the blood, such as lymphohematopoietic cancers, is the disruption of the normal pathways of cell cycle control. In lymphocytes a series of nonlinear biochemical cascades leads to cellular proliferation and also controls the production of cytokines that provide immunologic help (i.e., aid in B and T cell proliferation, maturation, and differentiation). These two distinct outcomes can be 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 production of cytokines, particularly interleukin-2, have been extensively characterized. It also is known that the fidelity of cell cycle progression is dependent on a regulatory network whose key components include cyclin-dependent kinases and cyclins. This review describes the current state of knowledge linking the antigen receptor response pathways and the activation of the cell cycle machinery in T cells.