IL-7/STAT5 cytokine signaling pathway is essential but insufficient for maintenance of naive CD4 T cell survival in peripheral lymphoid organs

Yoh Ichi Seki, Jianying Yang, Mariko Okamoto, Shinya Tanaka, Ryo Goitsuka, Michael A. Farrar, Masato Kubo

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Constitutive expression of suppressors of cytokine signaling (SOCS)1 in T lineage in vivo attenuated cytokine signaling and resulted in a dramatic reduction in the number of naive CD44lowCD62Lhigh CD4 T cells in the spleen. After adoptive transfer of thymocytes from SOCS1 transgenic mice into normal recipients, naive CD4 T cells rapidly disappeared from the spleen within 1 wk. Likewise, T cell-specific deletion of STAT5a/b in vivo resulted in a similar phenotype characterized by loss of naive CD4 T cells. Thus, STAT5-medlated signaling is crucial for promoting naive T cell survival. However, forced expression of constitatively active STAT5 failed to rescue CD4 T cells in SOCS1 transgenic mice, implying that STATS activation is necessary but not sufficient for naive CD4 T cell survival. Although blockade of the IL-7R, a SOCS1 target, resulted in clear inhibition of naive T cell survival, the effect occurred 3 wk after anti-IL-7R Ab treatment, but not at earlier time points. These results suggest that IL-7-mediated STAT5 activation is essential for long-term survival of naive CD4 cells after export from thymus, and that another SOCS1-sensitive cytokine is critical for short-term naive T cell survival.

Original languageEnglish
Pages (from-to)262-270
Number of pages9
JournalJournal of Immunology
Volume178
Issue number1
DOIs
Publication statusPublished - Jan 1 2007
Externally publishedYes

Fingerprint

Interleukin-7
Cell Survival
Maintenance
Cytokines
T-Lymphocytes
Transgenic Mice
Spleen
Adoptive Transfer
Thymocytes
Thymus Gland
Phenotype

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

IL-7/STAT5 cytokine signaling pathway is essential but insufficient for maintenance of naive CD4 T cell survival in peripheral lymphoid organs. / Seki, Yoh Ichi; Yang, Jianying; Okamoto, Mariko; Tanaka, Shinya; Goitsuka, Ryo; Farrar, Michael A.; Kubo, Masato.

In: Journal of Immunology, Vol. 178, No. 1, 01.01.2007, p. 262-270.

Research output: Contribution to journalArticle

Seki, Yoh Ichi ; Yang, Jianying ; Okamoto, Mariko ; Tanaka, Shinya ; Goitsuka, Ryo ; Farrar, Michael A. ; Kubo, Masato. / IL-7/STAT5 cytokine signaling pathway is essential but insufficient for maintenance of naive CD4 T cell survival in peripheral lymphoid organs. In: Journal of Immunology. 2007 ; Vol. 178, No. 1. pp. 262-270.
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