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

Nature Medicine volume 15, pages 914920 (2009) | Download Citation



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.

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We gratefully acknowledge A. Matsuoka, X. Yingda, E. Magoshi, M. Hayashi, K. Wakabayashi, M. Tajima and Y. Yamazaki for excellent technical assistance. This study was supported by Research Fellowships from the Japan Society for the Promotion of Science for Young Scientists (S.N.), Grants-in-Aid for Scientific Research (I.M., R.N.) and grants for Translational Systems Biology and Medicine Initiative (R.N., T.K.) and Global Centers of Excellence program (R.N., T.K.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan and a research grant from the National Institute of Biomedical Innovation (R.N.).

Author information


  1. Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

    • Satoshi Nishimura
    • , Ichiro Manabe
    • , Mika Nagasaki
    • , Hiroshi Yamashita
    •  & Ryozo Nagai
  2. Nano-Bioengineering Education Program, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

    • Satoshi Nishimura
    •  & Ichiro Manabe
  3. Translational Systems Biology and Medicine Initiative, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

    • Satoshi Nishimura
    • , Kohjiro Ueki
    • , Takashi Kadowaki
    •  & Ryozo Nagai
  4. PRESTO, Japan Science and Technology Agency, Kawaguchi, Japan.

    • Satoshi Nishimura
    •  & Ichiro Manabe
  5. Comprehensive Center of Education and Research for Chemical Biology of the Diseases, The University of Tokyo, Tokyo, Japan.

    • Ichiro Manabe
    • , Kohjiro Ueki
    • , Takashi Kadowaki
    •  & Ryozo Nagai
  6. Computational Diagnostic Radiology and Preventive Medicine, The University of Tokyo, Tokyo, Japan.

    • Mika Nagasaki
  7. Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

    • Koji Eto
    •  & Makoto Otsu
  8. Department of Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

    • Mitsuru Ohsugi
    • , Kazuo Hara
    • , Kohjiro Ueki
    •  & Takashi Kadowaki
  9. Department of Human and Engineered Environmental Studies, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.

    • Seiryo Sugiura
  10. Department of Plastic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

    • Kotaro Yoshimura


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S.N. and M.N. performed in vivo and in vitro assays and analyzed all of the end points. K.H., K.U. and K.Y. performed human subject assays. S.N., I.M., K.E., H.Y., M. Otsu, M. Ohsugi, S.S., T.K. and R.N. supervised entire studies. S.N. and I.M. wrote the manuscript.

Corresponding authors

Correspondence to Satoshi Nishimura or Ichiro Manabe.

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