CD8 + effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity

CD8 + effector T cells contribute to macrophage recruitment and adipose tissue inflammation in... Inflammation is increasingly regarded as a key process underlying metabolic diseases in obese individuals. In particular, obese adipose tissue shows features characteristic of active local inflammation. At present, however, little is known about the sequence of events that comprises the inflammatory cascade or the mechanism by which inflammation develops. We found that large numbers of CD8 + effector T cells infiltrated obese epididymal adipose tissue in mice fed a high-fat diet, whereas the numbers of CD4 + helper and regulatory T cells were diminished. The infiltration by CD8 + T cells preceded the accumulation of macrophages, and immunological and genetic depletion of CD8 + T cells lowered macrophage infiltration and adipose tissue inflammation and ameliorated systemic insulin resistance. Conversely, adoptive transfer of CD8 + T cells to CD8-deficient mice aggravated adipose inflammation. Coculture and other in vitro experiments revealed a vicious cycle of interactions between CD8 + T cells, macrophages and adipose tissue. Our findings suggest that obese adipose tissue activates CD8 + T cells, which, in turn, promote the recruitment and activation of macrophages in this tissue. These results support the notion that CD8 + T cells have an essential role in the initiation and propagation of adipose inflammation. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Medicine Springer Journals

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Publisher
Springer Journals
Copyright
Copyright © 2009 Nature Publishing Group
ISSN
1078-8956
eISSN
1546-170X
DOI
10.1038/nm.1964
pmid
19633658
Publisher site
See Article on Publisher Site

Abstract

Inflammation is increasingly regarded as a key process underlying metabolic diseases in obese individuals. In particular, obese adipose tissue shows features characteristic of active local inflammation. At present, however, little is known about the sequence of events that comprises the inflammatory cascade or the mechanism by which inflammation develops. We found that large numbers of CD8 + effector T cells infiltrated obese epididymal adipose tissue in mice fed a high-fat diet, whereas the numbers of CD4 + helper and regulatory T cells were diminished. The infiltration by CD8 + T cells preceded the accumulation of macrophages, and immunological and genetic depletion of CD8 + T cells lowered macrophage infiltration and adipose tissue inflammation and ameliorated systemic insulin resistance. Conversely, adoptive transfer of CD8 + T cells to CD8-deficient mice aggravated adipose inflammation. Coculture and other in vitro experiments revealed a vicious cycle of interactions between CD8 + T cells, macrophages and adipose tissue. Our findings suggest that obese adipose tissue activates CD8 + T cells, which, in turn, promote the recruitment and activation of macrophages in this tissue. These results support the notion that CD8 + T cells have an essential role in the initiation and propagation of adipose inflammation.

Journal

Nature MedicineSpringer Journals

Published: Jul 26, 2009

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