Hypoxia-Inducible Factor Regulates Survival of Antigen Receptor-Driven T Cells

Yuichi Makino, Hiroshi Nakamura, Eiji Ikeda, Kei Ohnuma, Kenji Yamauchi, Yutaka Yabe, Lorenz Poellinger, Yasunori Okada, Chikao Morimoto, Hirotoshi Tanaka

Research output: Contribution to journalArticle

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Abstract

Peripheral T lymphocytes undergo activation by antigenic stimulation and function in hypoxic areas of inflammation. We demonstrated in CD3-positive human T cells accumulating in inflammatory tissue expression of the hypoxia-inducible factor-1α (HIF-1α), indicating a role of hypoxia-mediated signals in regulation of T cell function. Surprisingly, accumulation of HIF-1α in human T cells required not only hypoxia but also TCR/CD3-mediated activation. Moreover, hypoxia repressed activation-induced cell death (AICD) by TCR/CD3 stimulation, resulting in an increased survival of the cells. Microarray analysis suggested the involvement of HIF-1 target gene product adrenomedullin (AM) in this process. Indeed, AM receptor antagonist abrogated hypoxia-mediated repression of AICD. Moreover, synthetic AM peptides repressed AICD even in normoxia. Taken together, we propose that hypoxia is a critical determinant of survival of the activated T cells via the HIF-1α-AM cascade, defining a previously unknown mode of regulation of peripheral immunity.

Original languageEnglish
Pages (from-to)6534-6540
Number of pages7
JournalJournal of Immunology
Volume171
Issue number12
Publication statusPublished - 2003 Dec 15

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Hypoxia-Inducible Factor 1
T-Cell Antigen Receptor
Adrenomedullin
T-Lymphocytes
Survival
Cell Death
Adrenomedullin Receptors
Cell Hypoxia
Microarray Analysis
Lymphocyte Activation
Immunity
Cell Survival
Hypoxia
Inflammation
Peptides
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Makino, Y., Nakamura, H., Ikeda, E., Ohnuma, K., Yamauchi, K., Yabe, Y., ... Tanaka, H. (2003). Hypoxia-Inducible Factor Regulates Survival of Antigen Receptor-Driven T Cells. Journal of Immunology, 171(12), 6534-6540.

Hypoxia-Inducible Factor Regulates Survival of Antigen Receptor-Driven T Cells. / Makino, Yuichi; Nakamura, Hiroshi; Ikeda, Eiji; Ohnuma, Kei; Yamauchi, Kenji; Yabe, Yutaka; Poellinger, Lorenz; Okada, Yasunori; Morimoto, Chikao; Tanaka, Hirotoshi.

In: Journal of Immunology, Vol. 171, No. 12, 15.12.2003, p. 6534-6540.

Research output: Contribution to journalArticle

Makino, Y, Nakamura, H, Ikeda, E, Ohnuma, K, Yamauchi, K, Yabe, Y, Poellinger, L, Okada, Y, Morimoto, C & Tanaka, H 2003, 'Hypoxia-Inducible Factor Regulates Survival of Antigen Receptor-Driven T Cells', Journal of Immunology, vol. 171, no. 12, pp. 6534-6540.
Makino Y, Nakamura H, Ikeda E, Ohnuma K, Yamauchi K, Yabe Y et al. Hypoxia-Inducible Factor Regulates Survival of Antigen Receptor-Driven T Cells. Journal of Immunology. 2003 Dec 15;171(12):6534-6540.
Makino, Yuichi ; Nakamura, Hiroshi ; Ikeda, Eiji ; Ohnuma, Kei ; Yamauchi, Kenji ; Yabe, Yutaka ; Poellinger, Lorenz ; Okada, Yasunori ; Morimoto, Chikao ; Tanaka, Hirotoshi. / Hypoxia-Inducible Factor Regulates Survival of Antigen Receptor-Driven T Cells. In: Journal of Immunology. 2003 ; Vol. 171, No. 12. pp. 6534-6540.
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