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

Resting T lymphocytes that have recognized antigen bound to a major hi stocompatibility complex molecule with the T-cell receptor require cos timulatory signals through accessory receptors, including CD2, CD4, CD 8, and CD28, for their clonal growth and expression of their functiona l repertoires. Absence of costimulation, in contrast, can induce clona l anergy in vitro and selective tolerance in vivo. Here we have define d a potential intracellular messenger for T-cell activation which is s trictly regulated by costimulatory signals mediated through accessory receptors: ppl9/cofilin, a small actin-binding protein, undergoes deph osphorylation and subsequent translocation from the cytosol into the n ucleus. In untransformed T cells this process correlates with function al responses essential for the induction of T-cell proliferation (i.e. , production of interleukin 2). Moreover, spontaneous dephosphorylatio n as well as nuclear translocation of ppl9/cofilin occur in the autono mously proliferating T-lymphoma cell line Jurkat.