CD4/CD8 lineage commitment: light at the end of the tunnel?

Two surprisingly clear results have emerged in the past year that suggest that the seemingly intractable problem of CD4/CD8 lineage commitment might eventually be resolved. Manipulating expression of the CD4 and CD8 coreceptors has long been a favorite method to examine the influence of T-cell receptor signalling on lineage commitment. An elegant new twist on this approach now shows that it is all a matter of timing. Thus, termination of CD4 expression after the initiation of positive selection is sufficient to cause complete redirection of class II-restricted thymocytes to the CD8 lineage, which strongly supports quantitative instructive models of lineage commitment. Progress in the field has been significantly hampered by ignorance of the underlying intracellular pathways. Two independent groups, which employed old-fashioned genetics versus new-fangled microarray technology, have now identified the same transcription factor, Th-POK, as a key regulator of alternate lineage commitment. The presence of this factor directs positively selected thymocytes to the CD4 lineage, whereas its absence causes default development to the CD8 lineage.