Authors:
Hilario J. Ramos, Ann M. Davis, Alexander G. Cole, John D. Schatzle, James Forman, and J. David Farrar
Summary:
Multiple innate signals regulate the genesis of effector and memory CD8+ T cells. In this study, we demonstrate that the innate cytokines interleukin (IL)–12 and interferon (IFN)–a/β regulate distinct aspects of effector and memory human CD8+ T-cell differentiation. IL-12 exclusively promoted the development of IFN-y– and tumor necrosis factor (TNF)–a–secreting T effector memory (TEM) cells, whereas IFN-a drove the development of T central memory (TCM) cells. The development of TEM and TCM was linked to cell division. In rapidly dividing cells, IL-12 programmed TEM through induction of the IL-12 receptor β2. In contrast, IFN-a regulated TCM development by slowing the progression of cell division in a subpopulation of cells that selectively expressed elevated IFN-a/β receptor-2. The strength of signal delivered through T-cell receptor (TCR) engagement regulated the responsiveness of cells to IL-12 and IFN-a. In the presence of both IL-12 and IFN-a, these cytokine signals were amplified as the strength of the TCR signal was increased, promoting the simultaneous development of both TCM and TEM. Together, our results support a novel model in which IL-12 and IFN-a act in a nonredundant manner to regulate the colinear generation of both effector and memory cells.
Source:
Blood; Vol. 113, No. 22, 5516-5525 (05/28/09)