The p38 mitogen-activated protein kinase regulates effector functions of primary human CD4 T cells

Eur J Immunol. 2005 Dec;35(12):3631-42. doi: 10.1002/eji.200535029.


The role of p38 mitogen-activated protein kinase in primary human T cells is incompletely understood. We analyzed in detail the role of p38 in the regulation of effector functions and differentiation of human CD4 T cells by using a p38-specific inhibitor and a dominant-negative mutant of p38. p38 was found to mediate expression of IL-10 and the Th2 cytokines IL-4, IL-5, and IL-13 in both, primary naive and memory T cells. In contrast, inhibition of p38 activity did not affect expression of the Th1 cytokines IFN-gamma and TNF induced by TCR-stimulation, but decreased IL-12-mediated IFN-gamma expression. Cytokine expression from established Th2 effector cells was also regulated by p38, however, the role of p38 was less pronounced compared to primary CD4 T cells. p38 MAPK regulated cytokine gene expression at both, the transcriptional level by activating gene transcription and the post-transcriptional level by stabilizing cytokine mRNA. As a result of the effect of p38 on IL-4 expression, p38 activity modulated differentiation of naive precursor T cells by inducing a shift of the Th1/Th2 balance toward the immuno-modulatory Th2 direction. Together, the data suggest that p38 plays a key role in human Th2 cell immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / enzymology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Humans
  • Immunologic Memory / physiology
  • Interleukin-4 / biosynthesis
  • Lymphocyte Activation / immunology
  • RNA Stability / immunology
  • RNA, Messenger / biosynthesis
  • Signal Transduction / physiology
  • Th2 Cells / metabolism
  • p38 Mitogen-Activated Protein Kinases / physiology*


  • Cytokines
  • RNA, Messenger
  • Interleukin-4
  • p38 Mitogen-Activated Protein Kinases