Stat5a regulates T helper cell differentiation by several distinct mechanisms

Citation
S. Kagami et al., Stat5a regulates T helper cell differentiation by several distinct mechanisms, BLOOD, 97(8), 2001, pp. 2358-2365
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Hematology,"Cardiovascular & Hematology Research
Journal title
BLOOD
ISSN journal
0006-4971 → ACNP
Volume
97
Issue
8
Year of publication
2001
Pages
2358 - 2365
Database
ISI
SICI code
0006-4971(20010415)97:8<2358:SRTHCD>2.0.ZU;2-4
Abstract
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 helpe r cell differentiation, we studied T helper (Th)1 and Th2 cell differentiat ion of Stat5a(-/-)CD4(+) T cells at single-cell levels. First, Th2 cell dif ferentiation from antigen-stimulated splenocytes was significantly decrease d in Stat5a(-/-) mice as compared with that in wild-type mice. Further, Th2 cell differentiation was also impaired in Stat5a(-/-) mice even when purif ied CD4(+) T cells were stimulated with anti-CD3 plus anti-CD28 antibodies in the presence of interleukin-4. Moreover, the retrovirus-mediated gene ex pression of Stat5a in Stat5a(-/-)CD4(+) T cells restored the Th2 cell diffe rentiation at the similar levels to that in wild-type CD4(+) T cells, In ad dition, 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 decr ease in the number of CD4(+)CD25(+) T cells in Stat5a(-/-) mice. Furthermor e, the depletion of CD4(+)CD25(+) T cells from wild-type splenocytes signif icantly decreased Th2 cell differentiation but increased Th1 cell different iation, whereas the depletion of CD4(+)CD25(+) T cells from Stat5a(-/-) spl enocytes had no significant effect on the Th1 and Th2 cell differentiation. Together, these results indicate that the intrinsic expression of Stat5a i n CD4(+) T cells is required for Th2 cell differentiation and that Stat5a i s involved in the development of CD4(+)CD25(+) immunoregulatory T cells tha t modulate T helper cell differentiation toward Th2 cells. (Blood, 2001;97: 2358-2365) (C) 2001 by The American Society of Hematology.