|
|
 Previous Article | Table of Contents | Next Article 
Blood, 15 April 2001, Vol. 97, No. 8, pp. 2358-2365
IMMUNOBIOLOGY
Stat5a regulates T helper cell differentiation by several
distinct mechanisms
Shin-ichiro Kagami,
Hiroshi Nakajima,
Akira Suto,
Koichi Hirose,
Kotaro Suzuki,
Sumiyo Morita,
Ikunoshin Kato,
Yasushi Saito,
Toshio Kitamura, and
Itsuo Iwamoto
From the Department of Internal Medicine II, Chiba
University School of Medicine, Japan; Department of Hematopoietic
Factors, The Institute of Medical Science, University of Tokyo, Japan;
and Takara Shuzo, Biotechnology Research Laboratories, Shiga, Japan.
We have previously shown that CD4+ T cell-mediated
allergic inflammation is diminished in signal transducer and activator
of transcription (Stat)5a-deficient (Stat5a /) mice. To
determine whether Stat5a regulates T helper cell differentiation, we
studied T helper (Th)1 and Th2 cell differentiation of
Stat5a/CD4+ T cells at single-cell levels.
First, Th2 cell differentiation from antigen-stimulated splenocytes was
significantly decreased in Stat5a/ mice as compared
with that in wild-type mice. Further, Th2 cell differentiation was also
impaired in Stat5a/ mice even when purified
CD4+ T cells were stimulated with anti-CD3 plus anti-CD28
antibodies in the presence of interleukin-4. Moreover, the
retrovirus-mediated gene expression of Stat5a in
Stat5a/CD4+ T cells restored the Th2 cell
differentiation at the similar levels to that in wild-type
CD4+ T cells. In addition, interleukin-4 normally
phosphorylated Stat6 in CD4+ T cells from
Stat5a/ mice. Second, the development of
CD4+CD25+ immunoregulatory T cells was impaired
in Stat5a/ mice, as indicated by a significant
decrease in the number of CD4+CD25+ T cells in
Stat5a/ mice. Furthermore, the depletion of
CD4+CD25+ T cells from wild-type splenocytes
significantly decreased Th2 cell differentiation but increased Th1 cell
differentiation, whereas the depletion of
CD4+CD25+ T cells from Stat5a/
splenocytes had no significant effect on the Th1 and Th2 cell differentiation. Together, these results indicate that the intrinsic expression of Stat5a in CD4+ T cells is required for Th2
cell differentiation and that Stat5a is involved in the development of
CD4+CD25+ immunoregulatory T cells that
modulate T helper cell differentiation toward Th2 cells.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. Furuta, S.-i. Kagami, T. Tamachi, K. Ikeda, M. Fujiwara, A. Suto, K. Hirose, N. Watanabe, Y. Saito, I. Iwamoto, et al.
Overlapping and Distinct Roles of STAT4 and T-bet in the Regulation of T Cell Differentiation and Allergic Airway Inflammation
J. Immunol.,
May 15, 2008;
180(10):
6656 - 6662.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Omori and S. Ziegler
Induction of IL-4 Expression in CD4+ T Cells by Thymic Stromal Lymphopoietin
J. Immunol.,
February 1, 2007;
178(3):
1396 - 1404.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Yagi, Y. Arimura, H. Takatori, H. Nakajima, I. Iwamoto, and T. Uchiyama
Genetic background influences Th cell differentiation by controlling the capacity for IL-2-induced IL-4 production by naive CD4+ T cells
Int. Immunol.,
December 1, 2006;
18(12):
1681 - 1690.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Toda and C. A. Piccirillo
Development and function of naturally occurring CD4+CD25+ regulatory T cells
J. Leukoc. Biol.,
September 1, 2006;
80(3):
458 - 470.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Suto, H. Nakajima, N. Tokumasa, H. Takatori, S.-i. Kagami, K. Suzuki, and I. Iwamoto
Murine Plasmacytoid Dendritic Cells Produce IFN-{gamma} upon IL-4 Stimulation
J. Immunol.,
November 1, 2005;
175(9):
5681 - 5689.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Yamane, J. Zhu, and W. E. Paul
Independent roles for IL-2 and GATA-3 in stimulating naive CD4+ T cells to generate a Th2-inducing cytokine environment
J. Exp. Med.,
September 19, 2005;
202(6):
793 - 804.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Takatori, H. Nakajima, S.-i. Kagami, K. Hirose, A. Suto, K. Suzuki, M. Kubo, A. Yoshimura, Y. Saito, and I. Iwamoto
Stat5a Inhibits IL-12-Induced Th1 Cell Differentiation through the Induction of Suppressor of Cytokine Signaling 3 Expression
J. Immunol.,
April 1, 2005;
174(7):
4105 - 4112.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Takatori, H. Nakajima, K. Hirose, S.-i. Kagami, T. Tamachi, A. Suto, K. Suzuki, Y. Saito, and I. Iwamoto
Indispensable Role of Stat5a in Stat6-Independent Th2 Cell Differentiation and Allergic Airway Inflammation
J. Immunol.,
March 15, 2005;
174(6):
3734 - 3740.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Cote-Sierra, G. Foucras, L. Guo, L. Chiodetti, H. A. Young, J. Hu-Li, J. Zhu, and W. E. Paul
Interleukin 2 plays a central role in Th2 differentiation
PNAS,
March 16, 2004;
101(11):
3880 - 3885.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Koyanagi, K.'i. Imanishi, Y. Arimura, H. Kato, J. Yagi, and T. Uchiyama
Immunologic immaturity, but high IL-4 productivity, of murine neonatal thymic CD4 single-positive T cells in the last stage of maturation
Int. Immunol.,
February 1, 2004;
16(2):
315 - 326.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. J. Mitchell, S. J. Whittaker, and S. John
Dysregulated Expression of COOH-Terminally Truncated Stat5 and Loss of IL2-Inducible Stat5-Dependent Gene Expression in Sezary Syndrome
Cancer Res.,
December 15, 2003;
63(24):
9048 - 9054.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. W. Snow, N. Abraham, M. C. Ma, B. G. Herndier, A. W. Pastuszak, and M. A. Goldsmith
Loss of Tolerance and Autoimmunity Affecting Multiple Organs in STAT5A/5B-Deficient Mice
J. Immunol.,
November 15, 2003;
171(10):
5042 - 5050.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Anderson, A. Sundstedt, L. Li, E. J. O'Neill, S. Li, D. C. Wraith, and P. Wang
Differential activation of signal transducer and activator of transcription (STAT)3 and STAT5 and induction of suppressors of cytokine signalling in Th1 and Th2 cells
Int. Immunol.,
November 1, 2003;
15(11):
1309 - 1317.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Thomas, R. Kumar, A. Preda-Pais, S. Casares, and T.-D. Brumeanu
A Model for Antigen-Specific T-Cell Anergy: Displacement of CD4-p56lck Signalosome from the Lipid Rafts by a Soluble, Dimeric Peptide-MHC Class II Chimera
J. Immunol.,
June 15, 2003;
170(12):
5981 - 5992.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Ikeda, H. Nakajima, K. Suzuki, S.-i. Kagami, K. Hirose, A. Suto, Y. Saito, and I. Iwamoto
Mast cells produce interleukin-25 upon Fcepsilon RI-mediated activation
Blood,
May 1, 2003;
101(9):
3594 - 3596.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Kunisato, S. Chiba, E. Nakagami-Yamaguchi, K. Kumano, T. Saito, S. Masuda, T. Yamaguchi, M. Osawa, R. Kageyama, H. Nakauchi, et al.
HES-1 preserves purified hematopoietic stem cells ex vivo and accumulates side population cells in vivo
Blood,
March 1, 2003;
101(5):
1777 - 1783.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Seto, H. Nakajima, A. Suto, K. Shimoda, Y. Saito, K. I. Nakayama, and I. Iwamoto
Enhanced Th2 Cell-Mediated Allergic Inflammation in Tyk2-Deficient Mice
J. Immunol.,
January 15, 2003;
170(2):
1077 - 1083.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Xu, H. Liu, M. Komai-Koma, C. Campbell, C. McSharry, J. Alexander, and F. Y. Liew
CD4+CD25+ Regulatory T Cells Suppress Differentiation and Functions of Th1 and Th2 Cells, Leishmania major Infection, and Colitis in Mice
J. Immunol.,
January 1, 2003;
170(1):
394 - 399.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Suto, H. Nakajima, K. Hirose, K. Suzuki, S.-i. Kagami, Y. Seto, A. Hoshimoto, Y. Saito, D. C. Foster, and I. Iwamoto
Interleukin 21 prevents antigen-induced IgE production by inhibiting germ line Cepsilon transcription of IL-4-stimulated B cells
Blood,
December 15, 2002;
100(13):
4565 - 4573.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. S. Hwang, I. A. White, and I-C. Ho
An IL-4-independent and CD25-mediated function of c-maf in promoting the production of Th2 cytokines
PNAS,
October 1, 2002;
99(20):
13026 - 13030.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Kunstle, J. Laine, G. Pierron, S.-i. Kagami, H. Nakajima, F. Hoh, C. Roumestand, M.-H. Stern, and M. Noguchi
Identification of Akt Association and Oligomerization Domains of the Akt Kinase Coactivator TCL1
Mol. Cell. Biol.,
March 1, 2002;
22(5):
1513 - 1525.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Suto, H. Nakajima, K. Ikeda, S. Kubo, T. Nakayama, M. Taniguchi, Y. Saito, and I. Iwamoto
CD4+CD25+ T-cell development is regulated by at least 2 distinct mechanisms
Blood,
January 15, 2002;
99(2):
555 - 560.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
