The Journal of Immunology, Vol 155, Issue 11 5234-5240, Copyright © 1995 by American Association of Immunologists

ARTICLES

Positive selection of thymocytes involves sustained interactions with the thymic microenvironment

RW Wilkinson, G Anderson, JJ Owen and EJ Jenkinson
Department of Anatomy/Center for Clinical Research in Immunology and Signaling, Medical School, University of Birmingham, United Kingdom.

CD4+8+ cortical thymocytes are critically dependent upon interaction with the thymic epithelium to undergo positive selection and maturation into single-positive CD4+ or CD8+ cells. Here we investigate further the nature of this interaction and provide evidence that positive selection requires sustained, rather than "single hit," interaction with thymic stromal cells. We also show that calcineurin-mediated signaling in thymocytes is required for the initial stages of positive selection, but is not essential throughout the period of thymocyte dependence on stromal cell contact during positive selection. In addition, we show that double-positive thymocytes that have initiated positive selection (CD69+4+8+) and newly generated single-positive (CD69+4+) cells differ markedly in response to the same stimulus through the TCR. The former undergo deletion, whereas the latter proliferate, indicating that a critical change in response to TCR ligation occurs within the narrow developmental window between these two stages.

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