?? T cells acquire effector fates in the thymus and differentiate into cytokine-producing effectors in a Listeria model of infection independently of CD28 costimulation.

ABSTRACT: Both antigen recognition and CD28 costimulation are required for the activation of naïve ?? T cells and their subsequent differentiation into cytokine-producing or cytotoxic effectors. Notably, this two-signal paradigm holds true for all ?? T cell subsets, regardless of whether they acquire their effector function in the periphery or the thymus. Because of contradictory results, however, it remains unresolved as to whether CD28 costimulation is necessary for ?? T cell activation and differentiation. Given that ?? T cells have been recently shown to acquire their effector fates in the thymus, it is conceivable that the contradictory results may be explained, in part, by a differential requirement for CD28 costimulation in the development or differentiation of each ?? T cell effector subset. To test this, we examined the role of CD28 in ?? T cell effector fate determination and function. We report that, although IFN?-producing ?? T (??-IFN?) cells express higher levels of CD28 than IL-17-producing ?? T (??-17) cells, CD28-deficiency had no effect on the thymic development of either subset. Also, following Listeria infection, we found that the expansion and differentiation of ??-17 and ??-IFN? effectors were comparable between CD28(+/+) and CD28(-/-) mice. To understand why CD28 costimulation is dispensable for ?? T cell activation and differentiation, we assessed glucose uptake and utilization by ?? T cells, as CD28 costimulation is known to promote glycolysis in ?? T cells. Importantly, we found that ?? T cells express higher surface levels of glucose transporters than ?? T cells and, when activated, exhibit effector functions over a broader range of glucose concentrations than activated ?? T cells. Together, these data not only demonstrate an enhanced glucose metabolism in ?? T cells but also provide an explanation for why ?? T cells are less dependent on CD28 costimulation than ?? T cells.

SUBMITTER: Laird RM 

PROVIDER: S-EPMC3650071 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature