Genetic background influences Th cell differentiation by controlling the capacity for IL-2-induced IL-4 production by naive CD4+ T cells

Int Immunol. 2006 Dec;18(12):1681-90. doi: 10.1093/intimm/dxl102. Epub 2006 Oct 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / genetics
  • Gene Expression Regulation*
  • Interleukin-2 / metabolism
  • Interleukin-2 / physiology*
  • Interleukin-4 / biosynthesis*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • STAT5 Transcription Factor / metabolism*
  • Species Specificity
  • T-Lymphocytes, Helper-Inducer / cytology*


  • Interleukin-2
  • STAT5 Transcription Factor
  • Interleukin-4