B7-CD28 Costimulatory Signals Control the Survival and Proliferation of Murine and Human gamma delta T Cells via IL-2 Production

作者：Ribot Julie C; deBarros Ana; Mancio Silva Liliana; Pamplona Ana; Silva Santos Bruno^*

来源：The Journal of Immunology, 2012, 189(3): 1202-1208.

DOI：10.4049/jimmunol.1200268

gamma delta T cells play key nonredundant roles in immunity to infections and tumors. Thus, it is critical to understand the molecular mechanisms responsible for gamma delta T cell activation and expansion in vivo. In striking contrast to their alpha beta counterparts, the costimulation requirements of gamma delta T cells remain poorly understood. Having previously described a role for the TNFR superfamily member CD27, we since screened for other nonredundant costimulatory receptors in gamma delta T cell activation. We report in this article that the Ig superfamily receptor CD28 (but not its related protein ICOS) is expressed on freshly isolated lymphoid gamma delta T cells and synergizes with the TCR to induce autocrine IL-2 production that promotes gamma delta cell survival and proliferation in both mice and humans. Specific gain-of-function and loss-of-function experiments demonstrated a nonredundant function for CD28 interactions with its B7 ligands, B7.1 (CD80) and B7.2 (CD86), both in vitro and in vivo. Thus, gamma delta cell proliferation was significantly enhanced by CD28 receptor agonists but abrogated by B7 Ab-mediated blockade. Furthermore, gamma delta cell expansion following Plasmodium infection was severely impaired in mice genetically deficient for CD28. This resulted in the failure to mount both IFN-gamma-mediated and IL-17-mediated gamma delta cell responses, which contrasted with the selective effect of CD27 on IFN-gamma-producing gamma delta cells. Our data collectively show that CD28 signals are required for IL-2-mediated survival and proliferation of both CD27(+) and CD27(-) gamma delta T cell subsets, thus providing new mechanistic insight for their modulation in disease models. The Journal of Immunology, 2012, 189: 1202-1208.

• 出版日期2012-8-1