COSTIMULATORY SIGNALS FOR HUMAN T-CELL ACTIVATION INDUCE NUCLEAR TRANSLOCATION OF PP19/COFILIN

Resting T lymphocytes that have recognized antigen bound to a major histocompatibility complex molecule with the T-cell receptor require costimulatory signals through accessory receptors, including CD2, CD4, CD8, and CD28, for their clonal growth and expression of their functional repertoires. Absence of costimulation, in contrast, can induce clonal anergy in vitro and selective tolerance in vivo. Here we have defined a potential intracellular messenger for T-cell activation which is strictly regulated by costimulatory signals mediated through accessory receptors: ppl9/cofilin, a small actin-binding protein, undergoes dephosphorylation and subsequent translocation from the cytosol into the nucleus. In untransformed T cells this process correlates with functional responses essential for the induction of T-cell proliferation (i.e., production of interleukin 2). Moreover, spontaneous dephosphorylation as well as nuclear translocation of ppl9/cofilin occur in the autonomously proliferating T-lymphoma cell line Jurkat.