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  • Title: In favor of the selective model of positive selection.
    Author: Chan SH, Benoist C, Mathis D.
    Journal: Semin Immunol; 1994 Aug; 6(4):241-8. PubMed ID: 8000033.
    Abstract:
    The mechanisms of thymocyte commitment towards the CD4+ and CD8+ lineage remain unresolved. Two models--one based on instruction, the other on selection--have previously been proposed. The instructional model has been popularly received based on results of earlier studies. However, our data from MHC class II, class I, and double-deficient mice suggest otherwise. There exists a significant population of CD4+ cells that is intermediate in maturity between CD4+ CD8+ and fully mature CD4+ CD8- thymocytes in class II-deficient animals; an analogous population of CD4-CD8+ cells exists in class I-negative mice. We suggest that a selective model in which two TCR-MHC molecule engagements are required: the first induces a random down-modulation of either CD4 or CD8 and some differentiation; the second, involving the participation of the appropriate coreceptor, permits end-stage differentiation.
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