Dec, 2006
Genetic background influences T-h cell differentiation by controlling the capacity for IL-2-induced IL-4 production by naive CD4(+) T cells
INTERNATIONAL IMMUNOLOGY
- ,
- ,
- ,
- ,
- ,
- Volume
- 18
- Number
- 12
- First page
- 1681
- Last page
- 1690
- Language
- English
- Publishing type
- Research paper (scientific journal)
- DOI
- 10.1093/intimm/dxl102
- Publisher
- OXFORD UNIV PRESS
Comparative studies using T(h)2-prone BALB/c and T(h)1-prone C57BL/6 mice were performed to clarify the influence of genetic background on T-h cell differentiation. The results showed IL-4, the production of which is induced by IL-2, to be much more abundantly produced by BALB/c naive CD4(+) T cells than by C57BL/6 naive CD4(+) T cells, thereby leading to a tendency for differentiation toward T(h)2 in BALB/c naive CD4(+) T cells. This difference in IL-4 production between the two naive CD4(+) T cells appeared to be attributable to specific intracellular signaling events. Signal transducer and activator of transcription 5 (STAT5) was preferentially activated by IL-2 in CD4(+) T cells developing in BALB/c in contrast to the corresponding cells in C57BL/6. In addition, IL-4 also induced stronger STAT5 activation in CD4(+) T cells developing in BALB/c than in those developing in C57BL/6, whereas STAT6 was equally activated in these two cells. Further results supported the involvement of STAT5 in the difference in T-h cell differentiation between BALB/c and C57BL/6 naive CD4(+) T cells. STAT5A(-/-) naive CD4(+) T cells with the BALB/c genetic background showed markedly less IL-2-induced IL-4 production than BALB/c naive CD4(+) T cells. Conversely, forced expression of the constitutively active forms of STAT5A and STAT5B in C57BL/6 naive CD4(+) T cells promoted the differentiation of T(h)2 cells. Thus, our results indicate IL-2-induced IL-4 production by naive CD4(+) T cells, in which STAT5 activation is involved and directly controlled by the genetic background, to influence T-h cell differentiation in murine strains.
- Link information
- ID information
-
- DOI : 10.1093/intimm/dxl102
- ISSN : 0953-8178
- Pubmed ID : 17035345
- Web of Science ID : WOS:000242716500007