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Precocious expression of T cell functional response genes in vivo in primitive thymocytes before T lineage commitment

Wang, Hua and Diamond, Rochelle A. and Yang-Snyder, Julia A. and Rothenberg, Ellen V. (1998) Precocious expression of T cell functional response genes in vivo in primitive thymocytes before T lineage commitment. International Immunology, 10 (11). pp. 1623-1635. ISSN 0953-8178. http://resolver.caltech.edu/CaltechAUTHORS:20120119-094044402

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Abstract

The genes encoding effector molecules of mature T cells, IL-2, perforin and IL-4, were found to be expressed in vivo in the most primitive subsets of thymocytes of adult mice. These subsets have previously been identified by their cell surface markers and by their expression of other T lineage-associated genes. While IL-2, perforin and IL-4 are expressed in distinct patterns, all three are expressed before the induction of RAG-1 and pre-TCR alpha mRNA expression, and are confined to subsets of cells that apparently have not yet undergone commitment to the T lineage. Thus, expression of T cell response genes appears to be one of the earliest markers of lymphocyte differentiation. Activation events marked by CD69 induction occur in these early cell types, but the response gene expression by these cells is separable from CD69 expression. IL-2 and perforin are induced again much later in thymocyte development, during TCR-dependent repertoire selection. At those stages, IL-2 protein and RNA levels per cell are higher, but the fraction of cells expressing IL-2 appears to be much lower than in the most immature stages. In addition, a striking feature of the immature populations is the robust IL-2 expression by presumptive immature NK cells. These findings are discussed in terms of the developmental origins of lineage specificity in T cell response gene regulation.


Item Type:Article
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http://dx.doi.org/10.1093/intimm/10.11.1623DOIUNSPECIFIED
http://intimm.oxfordjournals.org/content/10/11/1623PublisherUNSPECIFIED
Additional Information:© 1998 Oxford University Press. Received 14 April 1998, accepted 16 July 1998. Transmitting editor: H. R. MacDonald. We wish to thank Drs Ken Dorshking, Yoichi Shinkai, Fred Alt, Dawne Paige and Steve Hedrick for initially donating valuable breeding stocks of mice and providing some tissue samples used in these studies. We are particularly grateful to Patrick Koen, for valuable assistance with the flow cytometry: to Heidi Sikonia, Raymond Holz and Dana Miller, for assiduous care of the mutant mice; and to members of the Rothenberg laboraroty and of the Stowers Institute for Medical Research Consortium at Caltech for stimulating discussion and criticism. We also thank Bob Turring and the Caltech Photo Lab for valuable help with the figures. This work was supported by the Stowers Institute of Medical Research, by a grant from the State of California Tobacco-Related Disease Research Program (4ART-0624), and by two grants from the USPHS, AI34041 and AG13108. We are also glad to acknowledge the important assistance of the Caltech Biopolymer Synthesis Facility and the Caltech Flow Cytometry and Cell Sorting Facility, supported in part by the Beckman Institute at Caltech.
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Funding AgencyGrant Number
Stowers Institute for Medical ResearchUNSPECIFIED
California Tobacco-Related Disease Research Program4ART-0624
USPHSAI34041
USPHSAG13108
Caltech Beckman Institute UNSPECIFIED
Record Number:CaltechAUTHORS:20120119-094044402
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20120119-094044402
Official Citation:H Wang, R A Diamond, J A Yang-Snyder, and E V Rothenberg Precocious expression of T cell functional response genes in vivo in primitive thymocytes before T lineage commitment. Int. Immunol. (1998) 10(11): 1623-1635 doi:10.1093/intimm/10.11.1623
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:28851
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:19 Jan 2012 19:38
Last Modified:26 Dec 2012 14:42

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