+ STAT 5 Is Critical To Maintain Effector CD 8 Finkelman

During an immune response, most effector T cells die, whereas some are maintained and become memory T cells. Factors controlling the survival of effector CD4 + and CD8 + T cells remain unclear. In this study, we assessed the role of IL-7, IL-15, and their common signal transducer, STAT5, in maintaining effector CD4 + and CD8 + T cell responses. Following viral infection, IL-15 was required to maintain a subpopulation of effector CD8 + T cells expressing high levels of killer cell lectin-like receptor subfamily G, member 1 (KLRG1), and lower levels of CD127, whereas IL-7 and IL-15 acted together to maintain KLRG1 low CD127 high CD8 + effector T cells. In contrast, effector CD4 + T cell numbers were not affected by the individual or combined loss of IL-15 and IL-7. Both IL-7 and IL-15 drove phosphorylation of STAT5 within effector CD4 + and CD8 + T cells. When STAT5 was deleted during the course of infection, both KLRG1 high CD127 low and KLRG1 low CD127 high CD8 + T cells were lost, although effector CD4 + T cell populations were maintained. Furthermore, STAT5 was required to maintain expression of Bcl-2 in effector CD8 + , but not CD4 + , T cells. Finally, IL-7 and IL-15 required STAT5 to induce Bcl-2 expression and to maintain effector CD8 + T cells. Together, these data demonstrate that IL-7 and IL-15 signaling converge on STAT5 to maintain effector CD8 + T cell responses. M aintaining homeostasis of the T cell compartment is critical for normal immune system function. T cell homeostasis is altered during acute viral infection, when Ag-specific CD4 + and CD8 + T cells undergo massive expansion. Shortly thereafter, regulated induction of apoptosis, requiring the proapoptotic molecule, Bim, reduces the expanded T cell population and restores homeostasis (1, 2). Mechanism(s) that controls which effector cells die and which survive and become memory cells remains unclear. Recent work has shown that heterogeneity within the effector CD8 + T cell pool may allow for identification of some effector T cells with memory precursor properties. For example, after acute viral infection, effector CD8 + T cells having increased expression of killer cell lectin-like receptor subfamily G, member 1 (KLRG1), and decreased expression of CD127 (IL-7Ra) had a decreased propensity to generate memory T cells after adoptive transfer (3). Conversely, KLRG1 low CD127 high effector CD8 + T cells had more potential for …