T cells differentiate into T helper cells, which express CD4, or killer T cells, which express CD8. Although several genes have been implicated in this cell-fate decision, He et al. report that lack of functional transcription factor Th-POK (T helper-inducing POZ/Krüppel factor) results in complete conversion of CD4+ cells to CD8+ cells. He et al. studied a spontaneously arising recessive mouse mutant (HD) that did not form CD4+ T cells, cloned the responsible gene, and identified the mutation (an Arg to Gly switch in the putative DNA binding region). They used various genetic methods to show that forced expression of CD4 did not produce CD4+ cells and that loss of CD8 did not allow the formation of CD4+ cells in the absence of functional Th-POK. Real-time reverse transcription polymerase chain reaction (RT-PCR) of wild-type thymic cells showed that Th-POK expression was restricted to CD4+ and T cells at an intermediate stage of development (CD4+CD8lo). Forced expression of Th-POK in bone marrow cells resulted in formation of CD4+ cells exclusively. Thus, Th-POK appears to be necessary and sufficient for formation of the T helper cell type. To quote Robey, "Th-POK seems to be at the top of a gene-regulation hierarchy that controls T-cell fate."
X. He, X. He, V. P. Dave, Y. Zhang, X. Hua, E. Nicolas, W. Xu, B. A. Roe, D. J. Kappes, The zinc finger transcription factor Th-POK regulates CD4 versus CD8 T-cell lineage commitment. Nature 433, 826-833 (2005). [PubMed]
E. A. Robey, Guide for a cell-fate decision. Nature 433, 813-814 (2005). [PubMed]