Abstract
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. IFNγ 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 229-237 |
| Number of pages | 9 |
| Journal | Immunity |
| Volume | 9 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 1998 |
Funding
All animal use conformed to the University of Chicago’s Institutional Animal Care and Use Protocols. This work was supported by the National Institutes of Health (AI-42370). S. L. R. is a recipient of a Burroughs Wellcome Fund New Investigator Award in Molecular Parasitology. We are grateful to C. Thompson, R. Seder, U. Storb, A. Mahowald, D. Gottschling, M. Elloso, A. Wells, S. Kron, A. Koff, E. Smith, and C. Brown for helpful discussion, A. Minn for excellent suggestions, S. Rose and E. Travis for assistance, M. Grusby for providing STAT-6-deficient mice, and N. Noben-Trauth for the IL-4 probe.
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases
