A mandatory role for STAT4 in IL-12 induction of mouse T cell CCR5

M. Iwasaki, T. Mukai, C. Nakajima, Y. F. Yang, P. Gao, N. Yamaguchi, M. Tomura, H. Fujiwara, T. Hamaoka

Research output: Contribution to journalArticlepeer-review

Abstract

IL-12 was recently shown to induce CCR5 on TCR-triggered mouse T cells. Considering that STAT4 is the most critical of IL-12 signaling molecules, this study investigated the role for STAT4 in the induction of CCR5 expression. IL-12R was induced by stimulation with anti-CD3 plus anti-CD28 mAb similarly on T cells from wild-type (WT) and STAT4-deficient (STAT4-/-) mice, but the levels of IL-12R induced on IFN-γ-deficient (IFN-γ-/-) T cells were lower compared with WT T cells. Exposure of TCR-triggered WT T cells to IL-12 induced CCR5 expression. In contrast, TCR-triggered STAT4-/- T cells failed to express CCR5 in response to IL-12. IL-12 stimulation induced detectable albeit reduced levels of CCR5 expression on IFN-γ-/- T cells. Addition of rIFN-γ to cultures of IFN-γ-/- T cells, particularly to cultures during TCR triggering resulted in restoration of CCR5 expression. However, CCR5 expression was not induced in STAT4-/- T cells by supplementation of rIFN-γ. These results indicate that for the induction of CCR5 on T cells, 1) STAT4 plays an indispensable role; 2) such a role is not substituted by simply supplementing rIFN-γ; and 3) IFN-γ amplifies CCR5 induction depending on the presence of STAT4.

Original languageEnglish (US)
Pages (from-to)6877-6883
Number of pages7
JournalJournal of Immunology
Volume167
Issue number12
DOIs
StatePublished - Dec 15 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'A mandatory role for STAT4 in IL-12 induction of mouse T cell CCR5'. Together they form a unique fingerprint.

Cite this