Helper T cell differentiation is controlled by the cell cycle

Immunity. 1998 Aug;9(2):229-37. doi: 10.1016/s1074-7613(00)80605-6.


Helper T (Th) cell differentiation is highly regulated by cytokines but initiated by mitogens. By examining gene expression in discrete generations of dividing cells, we have delineated the relationship between proliferation and differentiation. Initial expression of IL-2 is cell cycle-independent, whereas effector cytokine expression is cell cycle-dependent. IFNgamma expression increases in frequency with successive cell cycles, while IL-4 expression requires three cell divisions. Cell cycle progression and cytokine signaling act in concert to relieve epigenetic repression and can be supplanted by agents that hyperacetylate histones and demethylate DNA. Terminally differentiated cells exhibit stable epigenetic modification and cell cycle-independent gene expression. These data reveal a novel mechanism governing Th cell fate that initially integrates proliferative and differentiative signals and subsequently maintains stability of the differentiated state.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Cycle / physiology
  • Cell Differentiation / genetics
  • Cell Lineage / genetics
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Cytokines / physiology
  • Gene Expression / genetics
  • Immunologic Memory / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Signal Transduction / genetics
  • T-Lymphocytes, Helper-Inducer / cytology*
  • T-Lymphocytes, Helper-Inducer / metabolism


  • Cytokines