Cell-cycle regulation of T-cell responses--novel approaches to the control of alloimmunity.

Alloreactive T cells undergo clonal expansion before they participate in allograft rejection. Current estimates suggest that roughly 1 in 20 peripheral T cells are alloreactive, and these cells may expand at least 20-50-fold during an alloimmune response in vivo. The majority of immunosuppressive drugs currently used to facilitate graft survival in experimental models and in the clinic act to inhibit T-cell proliferation. This review focuses on 1) recent advances in monitoring alloreactive T-cell proliferation during alloimmune responses, 2) the link between cell division, anergy avoidance, and effector T-cell differentiation, and 3) an overview of growth factor receptor-coupled signal transduction pathways, with emphasis on key cell-cycle regulators that may serve as potential targets for novel immunosuppressive or tolerance-inducing strategies.