Responses to LCMV in mice revealed that early after infection, CD8+ T cells that intrinsically produced IL-2 were enriched in the memory pool. When compared to non-IL-2 producing CD8+ cells, these cells more rapidly adopted a memory phenotype upon adoptive transfer and were more resistant to exhaustion after chronic virus challenge. Intrinsic IL-2 production was associated with attenuated IL-2-dependant STAT5 signaling – a finding consistent with the observed skew towards preservation of memory, and away from effector function and terminal differentiation. These studies implicate intrinsic IL-2 in the early bifurcation of CD8+ T cell memory and effector functions.
Contributed by Margot O’Toole
ABSTRACT: Here, we show that the capacity to manufacture IL-2 identifies constituents of the expanded CD8 T cell effector pool that display stem-like features, preferentially survive, rapidly attain memory traits, resist exhaustion, and control chronic viral challenges. The cell-intrinsic synthesis of IL-2 by CD8 T cells attenuates the ability to receive IL-2-dependent STAT5 signals, thereby limiting terminal effector formation, endowing the IL-2-producing effector subset with superior protective powers. In contrast, the non-IL-2-producing effector cells respond to IL-2 signals and gain effector traits at the expense of memory formation. Despite having distinct properties during the effector phase, IL-2-producing and nonproducing CD8 T cells appear to converge transcriptionally as memory matures to form populations with equal recall abilities. Therefore, the potential to produce IL-2 during the effector, but not memory stage, is a consequential feature that dictates the protective capabilities of the response.
Author Info: (1) Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. (2) Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL
Author Info: (1) Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. (2) Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. (3) Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. (4) Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. (5) Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. (6) Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA. (7) Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. (8) Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. (9) Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
