CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity.
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.
Nishimura
Satoshi
S
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. snishi-tky@umin.ac.jp
Manabe
Ichiro
I
Nagasaki
Mika
M
Eto
Koji
K
Yamashita
Hiroshi
H
Ohsugi
Mitsuru
M
Otsu
Makoto
M
Hara
Kazuo
K
Ueki
Kohjiro
K
Sugiura
Seiryo
S
Yoshimura
Kotaro
K
Kadowaki
Takashi
T
Nagai
Ryozo
R
D017667:Adipocytes / Q000502:physiology; D000273:Adipose Tissue / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D002465:Cell Movement / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004036:Diet, Atherogenic; D015536:Down-Regulation; D007249:Inflammation / Q000097:blood / Q000276:immunology*; D018655:Lymphocyte Count; D008264:Macrophages / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000097:blood / Q000209:etiology / Q000276:immunology*