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CD4-CD8 lineage commitment: an inside view

Nature Immunology volume 6, pages 761–766 (2005)Cite this article

Abstract

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'.

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Figure 1: Thymocyte subset distribution and developmental pathways followed by MHC class I–restricted and MHC class II–restricted thymocytes in wild-type mice.
Figure 2: Instructive and stochastic-selective models of lineage commitment.
Figure 3: Inactivation or ectopic expression of Th-POK exerts opposing effects on lineage commitment.
Figure 4: Model of Th-POK-mediated control of lineage commitment.
Figure 5: Proposed functions of key molecules affecting CD4 and CD8 development.

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Acknowledgements

We thank the colleagues whose work could not be cited because of space constraints. Supported by the National Institutes of Health (D.J.K.) and the Commonwealth of Pennsylvania.

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  1. Fox Chase Cancer Center, Philadelphia, 19111, Pennsylvania, USA

    Dietmar J Kappes, Xiao He & Xi He

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Kappes, D., He, X. & He, X. CD4-CD8 lineage commitment: an inside view. Nat Immunol 6, 761–766 (2005). https://doi.org/10.1038/ni1230

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