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Curr Opin Immunol. 2002 Apr;14(2):207-15.

New perspectives on a developmental dilemma: the kinetic signaling model and the importance of signal duration for the CD4/CD8 lineage decision.

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Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA.


Double-positive thymocytes are short-lived bipotential cells whose developmental fate is determined by the specificity of their TCRs. A relatively small number of double-positive thymocytes undergo positive selection in the thymus and these are signaled to differentiate either into CD4(+) or CD8(+) mature T cells. The mechanism by which double-positive thymocytes determine their appropriate CD4/CD8 fate has been the subject of intense theoretical debate and rigorous experimental analysis. In the last year, 'signal duration' has been offered as a replacement for 'signal strength' as a major determinant of the CD4/CD8 decision, a deceptively minor refinement that requires a major change in our understanding of how signaled double-positive thymocytes differentiate into mature T cells. Indeed, the kinetic signaling model provides a radically new perspective on the mechanism by which the CD4/CD8 lineage decision is made.

[Indexed for MEDLINE]

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