Essential Role of CD11a in CD8+ T-Cell Accumulation and Activation in Adipose Tissue

Objective-T cells, particularly CD8(+) T cells, are major participants in obesity-linked adipose tissue (AT) inflammation. We examined the mechanisms of CD8(+) T-cell accumulation and activation in AT and the role of CD11a, a beta 2 integrin. Approach and Results-CD8(+) T cells in AT of obese mice showed activated phenotypes with increased proliferation and interferon-gamma expression. In vitro, CD8(+) T cells from mouse AT displayed increased interferon-gamma expression and proliferation to stimulation with interleukin-12 and interleukin-18, which were increased in obese AT. CD11a was upregulated in CD8(+) T cells in obese mice. Ablation of CD11a in obese mice dramatically reduced T-cell accumulation, activation, and proliferation in AT. Adoptive transfer showed that CD8(+) T cells from wild-type mice, but not from CD11a-deficient mice, infiltrated into AT of recipient obese wild-type mice. CD11a deficiency also reduced tumor necrosis factor-alpha-producing and interleukin-12-producing macrophages in AT and improved insulin resistance. Conclusions-Combined action of cytokines in obese AT induces proliferative response of CD8(+) T cells locally, which, along with increased infiltration, contributes to CD8(+) T-cell accumulation and activation in AT. CD11a plays a crucial role in AT inflammation by participating in T-cell infiltration and activation.