| First Author | Laird RM | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 5 | Pages | e63178 |
| PubMed ID | 23671671 | Mgi Jnum | J:200526 |
| Mgi Id | MGI:5508820 | Doi | 10.1371/journal.pone.0063178 |
| Citation | Laird RM, et al. (2013) gammadelta T cells acquire effector fates in the thymus and differentiate into cytokine-producing effectors in a listeria model of infection independently of CD28 costimulation. PLoS One 8(5):e63178 |
| abstractText | Both antigen recognition and CD28 costimulation are required for the activation of naive alphabeta T cells and their subsequent differentiation into cytokine-producing or cytotoxic effectors. Notably, this two-signal paradigm holds true for all alphabeta 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 gammadelta T cell activation and differentiation. Given that gammadelta 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 gammadelta T cell effector subset. To test this, we examined the role of CD28 in gammadelta T cell effector fate determination and function. We report that, although IFNgamma-producing gammadelta T (gammadelta-IFNgamma) cells express higher levels of CD28 than IL-17-producing gammadelta T (gammadelta-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 gammadelta-17 and gammadelta-IFNgamma effectors were comparable between CD28(+/+) and CD28(-/-) mice. To understand why CD28 costimulation is dispensable for gammadelta T cell activation and differentiation, we assessed glucose uptake and utilization by gammadelta T cells, as CD28 costimulation is known to promote glycolysis in alphabeta T cells. Importantly, we found that gammadelta T cells express higher surface levels of glucose transporters than alphabeta T cells and, when activated, exhibit effector functions over a broader range of glucose concentrations than activated alphabeta T cells. Together, these data not only demonstrate an enhanced glucose metabolism in gammadelta T cells but also provide an explanation for why gammadelta T cells are less dependent on CD28 costimulation than alphabeta T cells. |
