Abstract 138: Deficiency of CD11a Reduces CD8+ T-Cell Activation and Proliferation in Adipose Tissue of Obese Mice
T cells, particularly CD8+ T cells, are major participants in obesity-linked adipose tissue (AT) inflammation. CD11a, a β2-integrin, is crucial for T cell adhesion and interactions with antigen-presenting cells. It has been shown that stimulation of CD11a lowered the threshold of T cell activation, yet the role of CD11a in T cell activation in AT remains unknown. We used CD11a-/- mice to test the hypothesis that CD11a deficiency reduces CD8+ T cell activation in AT. Mice fed high-fat diet for 3 months were used as an obesity model, with mice on normal diet as lean controls. CD8+ T cells and related cytokines were examined in AT by flow cytometry or quantitative RT-PCR. Compared to lean wild-type (WT) mice, obese WT mice had increased numbers of activated CD8+ T cells, with higher proportions of CD11ahighCD8+ memory T cells, CD44+CD62L- effector memory CD8+ T cells and CD44+CD69+ effector CD8+ T cells; and increased mRNA levels of granzyme B and IFN-γ in AT. Compared to obese WT, obese CD11a-/- mice had lower proportions of CD44+CD62L- effector memory CD8+ T cells and CD44+CD69+ effector CD8+ T cells, and decreased mRNA levels of granzyme B and IFN-γ (P<0.01), implying decreased activation of CD8+ T cells. IL-2, IL-12 and IL-18 levels were increased in AT of obese WT compared to that of leans, and were lower in AT of obese CD11a-/- mice than that of obese WT. In vitro treatment with IL-2, IL-12 and IL-18 induced proliferation and expression of IFN-γ and CD69 in CD8+ cells isolated from AT of WT mice. Compared to those from WT mice, CD8+ T cells from AT of CD11a-/- mice showed decreased response to cytokine stimulation with fewer cells expressing IFN-γ (7.0±1.1% in CD11a-/- vs. 11.3±1.1% in WT, n=3-5/group, P<0.05). In addition, using Edu labeling techniques, we studied proliferation of CD8+ T cells in AT in vivo. At 3 hours after intraperitoneal injection of Edu, no Edu+ T cells appeared in blood but we found CD8+/Edu+ T cells in AT of WT mice, indicating CD8+ T cells proliferated in AT. Compared to obese WT mice, obese CD11a-/- mice had decreased proportion of proliferating CD8+ T cells in AT (1.3±0.4% in CD11a-/- vs. 2.4±0.1% in WT, n=3/group, P<0.01). In conclusion, we demonstrated that CD11a played a crucial role in CD8+ T cell activation and proliferation in AT associated with obesity.
- © 2012 by American Heart Association, Inc.