Functional heterogeneity of the CD8 T cell response: implications for fate and memory formation (LYM4P.746)

Abstract

Abstract Although anti-viral CD8 T cells display differences in their portfolios of effector functions, dissecting this ensemble has been impeded by the lack of effective methods for segregating, tracking, and defining these distinct subsets based upon their cytokine production profiles. To address this we utilized novel IL-2 and IFN-γ double cytokine reporter mice. We demonstrated that within 6 hours of activation naïve CD8 T cells undergo a burst of cytokine production and populations are detectable that produce only IL-2, only IFN-γ, co-produce IL-2 and IFN-γ, or do not produce either cytokine. These patterns of cytokine production are reconfigured by changes in the inflammatory milieu. As effector and memory CD8 T cells develop a shift towards IFN-γ production occurs, with a smaller subset capable of co-producing IL-2 and IFN-γ, and the IL-2 only population typically not detectable. By harnessing the cytokine reporter system to separate viable IL-2+ and IL-2- effector subsets, and conducting a series of adoptive transfer studies, we discovered that IL-2 producing effector CD8 T cells transition into memory populations that rapidly and vigorously proliferative upon secondary challenge. Taken together these studies illustrate that dissecting the functional complexity of CD8 T cells has the potential to pin-point the properties that enable these cells to thrive and form the memory compartment, and reveal possible biomarkers of successful responses.