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Arterioscler Thromb Vasc Biol. 2014 Jan;34(1):34-43. doi: 10.1161/ATVBAHA.113.302077. Epub 2013 Oct 24.

Essential role of CD11a in CD8+ T-cell accumulation and activation in adipose tissue.

Author information

1
From the Departments of Medicine (E.J., X.D.P., D.Y., I.M.K., J.L.P., C.M.B., H.W.) and Pediatrics (C.W.S., C.M.B., H.W.), Baylor College of Medicine, Houston, TX; and Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, The Methodist Hospital, Houston, TX (C.M.B.).

Abstract

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 β2 integrin.

APPROACH AND RESULTS:

CD8(+) T cells in AT of obese mice showed activated phenotypes with increased proliferation and interferon-γ expression. In vitro, CD8(+) T cells from mouse AT displayed increased interferon-γ 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-α-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.

KEYWORDS:

adipose tissue; inflammation; insulin resistance; obesity

PMID:
24158516
PMCID:
PMC4060534
DOI:
10.1161/ATVBAHA.113.302077
[Indexed for MEDLINE]
Free PMC Article

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