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 journalArticle

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
StatePublished - Dec 15 2001
Externally publishedYes

Fingerprint

Interleukin-12
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Iwasaki, M., Mukai, T., Nakajima, C., Yang, Y. F., Gao, P., Yamaguchi, N., ... Hamaoka, T. (2001). A mandatory role for STAT4 in IL-12 induction of mouse T cell CCR5. Journal of Immunology, 167(12), 6877-6883.

A mandatory role for STAT4 in IL-12 induction of mouse T cell CCR5. / Iwasaki, M.; Mukai, T.; Nakajima, C.; Yang, Y. F.; Gao, P.; Yamaguchi, N.; Tomura, M.; Fujiwara, H.; Hamaoka, T.

In: Journal of Immunology, Vol. 167, No. 12, 15.12.2001, p. 6877-6883.

Research output: Contribution to journalArticle

Iwasaki, M, Mukai, T, Nakajima, C, Yang, YF, Gao, P, Yamaguchi, N, Tomura, M, Fujiwara, H & Hamaoka, T 2001, 'A mandatory role for STAT4 in IL-12 induction of mouse T cell CCR5', Journal of Immunology, vol. 167, no. 12, pp. 6877-6883.
Iwasaki M, Mukai T, Nakajima C, Yang YF, Gao P, Yamaguchi N et al. A mandatory role for STAT4 in IL-12 induction of mouse T cell CCR5. Journal of Immunology. 2001 Dec 15;167(12):6877-6883.
Iwasaki, M. ; Mukai, T. ; Nakajima, C. ; Yang, Y. F. ; Gao, P. ; Yamaguchi, N. ; Tomura, M. ; Fujiwara, H. ; Hamaoka, T. / A mandatory role for STAT4 in IL-12 induction of mouse T cell CCR5. In: Journal of Immunology. 2001 ; Vol. 167, No. 12. pp. 6877-6883.
@article{3bee0dab98424f1f850c5967edd08a5e,
title = "A mandatory role for STAT4 in IL-12 induction of mouse T cell CCR5",
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.",
author = "M. Iwasaki and T. Mukai and C. Nakajima and Yang, {Y. F.} and P. Gao and N. Yamaguchi and M. Tomura and H. Fujiwara and T. Hamaoka",
year = "2001",
month = "12",
day = "15",
language = "English (US)",
volume = "167",
pages = "6877--6883",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "12",

}

TY - JOUR

T1 - A mandatory role for STAT4 in IL-12 induction of mouse T cell CCR5

AU - Iwasaki, M.

AU - Mukai, T.

AU - Nakajima, C.

AU - Yang, Y. F.

AU - Gao, P.

AU - Yamaguchi, N.

AU - Tomura, M.

AU - Fujiwara, H.

AU - Hamaoka, T.

PY - 2001/12/15

Y1 - 2001/12/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0035893018&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035893018&partnerID=8YFLogxK

M3 - Article

C2 - 11739505

AN - SCOPUS:0035893018

VL - 167

SP - 6877

EP - 6883

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 12

ER -