Stat5a regulates T helper cell differentiation by several distinct mechanisms

被引:74
作者
Kagami, S
Nakajima, H
Suto, A
Hirose, K
Suzuki, K
Morita, S
Kato, I
Saito, Y
Kitamura, T
Iwamoto, I
机构
[1] Chiba Univ, Sch Med, Dept Internal Med 2, Chiba 2608670, Japan
[2] Univ Tokyo, Inst Med Sci, Dept Hamatopoiet Factors, Tokyo, Japan
[3] Takara Shuzo Co Ltd, Biotechnol Res Labs, Shiga, Japan
关键词
D O I
10.1182/blood.V97.8.2358
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (Blood, 2001;97:2358-2365) (C) 2001 by The American Society of Hematology.
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页码:2358 / 2365
页数:8
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