K. Yasutomo et al., The duration of antigen receptor signalling determines CD4(+) versus CD8(+) T-cell lineage fate, NATURE, 404(6777), 2000, pp. 506-510
Signals elicited by binding of the T-cell antigen receptor and the CD4/CD8
co-receptor to major histocompatibility complex (MHC) molecules control the
generation of CD4(+) (helper) or CD8(+) (cytotoxic) T cells from thymic pr
ecursors that initially express both co-receptor proteins'. These precursor
s have unique, clonally distributed T-cell receptors with unpredictable spe
cificity for the self-MHC molecules involved in this differentiation proces
s', However, the mature T cells that emerge express only the CD4 (MHC class
II-binding) or CD8 (MHC class I-binding) co-receptor that complements the
MHC class-specificity of the T-cell receptor. How this matching of co-recep
tor-defined lineage and T-cell-receptor specificity is achieved remains unk
nown(1,3,4), as does whether signalling by the T-cell receptors, co-recepto
rs and/ or general cell-fate regulators such as Notch-1 (refs 5, 6) contrib
utes to initial lineage choice, to subsequent differentiation processes or
to both. Here we show that the CD4 versus CD8 lineage fate of immature thym
ocytes is controlled by the co-receptor-influenced duration of initial T-ce
ll receptor-dependent signalling. Notch-1 does not appear to be essential f
or this fate determination, but it is selectively required for CD8(+) T-cel
l maturation after commitment directed by T-cell receptors, This indicates
that the signals constraining CD4 versus CD8 lineage decisions are distinct
from those that support subsequent differentiation events such as silencin
g of co-receptor loci.