CD4-CD8 lineage commitment: an inside view.
The mechanism of CD4-CD8 lineage commitment, which ensures the correlation between T cell receptor specificity and adoption of the T killer or T helper phenotype, has long been the subject of intense debate. Various approaches are slowly elucidating the underlying molecular pathways. Analysis of the function of T cell receptor signaling (the 'top-down' approach) supports the view that differences in signal strength and/or duration 'instruct' alternative commitment. Analysis of the transcriptional regulation of the genes encoding CD4 and CD8 (the 'bottom-up' approach) has identified critical cis-acting elements and their interacting factors. Finally, identification of the transcription factor Th-POK as a central component of the CD4 lineage-determining pathway has provided a new starting point from which to unravel this intriguing process 'from the inside out'.
Kappes
Dietmar J
DJ
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. dj_kappes@fccc.edu
He
Xiao
X
He
Xi
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D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation; D019070:Cell Lineage; D002843:Chromatin / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology*; D008954:Models, Biological; D018448:Models, Immunological; D010641:Phenotype; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D002843:Chromatin; D014157:Transcription Factors; C497211:Zbtb7b protein, mouse