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.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
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.
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U2 - 10.4049/jimmunol.167.12.6877
DO - 10.4049/jimmunol.167.12.6877
M3 - Article
C2 - 11739505
AN - SCOPUS:0035893018
SN - 0022-1767
VL - 167
SP - 6877
EP - 6883
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -