Document 0520 DOCN M9620520 TI Positive selection of thymocytes involves sustained interactions with the thymic microenvironment. DT 9602 AU Wilkinson RW; Anderson G; Owen JJ; Jenkinson EJ; Department of Anatomy/Center for Clinical Research in Immunology; and Signaling, Medical School, University of Birmingham, United; Kingdom. SO J Immunol. 1995 Dec 1;155(11):5234-40. Unique Identifier : AIDSLINE MED/96072798 AB 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. DE Animal Antigens, CD/IMMUNOLOGY Antigens, Differentiation, T-Lymphocyte/IMMUNOLOGY Cell Differentiation/PHYSIOLOGY Clonal Deletion CD4-Positive T-Lymphocytes/*CYTOLOGY/IMMUNOLOGY CD8-Positive T-Lymphocytes/*CYTOLOGY/IMMUNOLOGY Epithelium/PHYSIOLOGY Mice Mice, Inbred BALB C Stromal Cells/PHYSIOLOGY Superantigens/IMMUNOLOGY Support, Non-U.S. Gov't Thymus Gland/*CYTOLOGY/EMBRYOLOGY/GROWTH & DEVELOPMENT/IMMUNOLOGY JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).