The lineage decisions of helper T cells

Abstract

Helper T (T_H)-cell differentiation is remarkably plastic, with many extrinsic signals affecting the balance of effector subsets. The role of cytokines as a purely instructive signal, causing undifferentiated cells to express new genes, is being re-examined. Among the newly recognized functions are the abilities of cytokines to mediate selective growth or survival and to repress the transcription of lineage-determining activators of the opposing fate. Epigenetic effects seem to have a crucial role in organizing T_H-cell differentiation. Some genes are induced by chromatin remodelling, which is a heritable trait of differentiated cells. CpG demethylation of cytokine loci might be an imprinting mechanism that ensures the heritability of the expressing state. Gene silencing seems to contribute to differentiation in at least two ways. The transcription of lineage-determining activator genes seems to become heritably silenced and their target cytokine loci seem to undergo physical repositioning in terminally differentiated cells of the opposing fate.