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Functional commitment to helper T cell lineage precedes positive selection and is independent of T cell receptor MHC specificity

Corbella, Paola and Moskophidis, Demetrius and Spanopoulou, Eugenia and Mamalaki, Clio and Tolaini, Mauro and Itano, Andrea and Lans, Deborah and Baltimore, David and Robeyj, Ellen and Kioussis, Dimitris (1994) Functional commitment to helper T cell lineage precedes positive selection and is independent of T cell receptor MHC specificity. Immunity, 1 (4). pp. 269-276. ISSN 1074-7613. https://resolver.caltech.edu/CaltechAUTHORS:20200513-080630337

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Abstract

Thymocyte differentiation proceeds from double positive CD4⁺CD8⁺ to single positive T cells. It has been proposed that this process occurs by an instructive or a stochastic mechanism. In this report, we show that in recombination-deficient mice (RAG-1^(-/-)) constitutive expression of a CD8 transgene allows maturation of CD4⁺ (CD8tg⁺) cells, which express mature levels of a transgenic class I-restricted T cell receptor, F5. Rescued F5⁺CD4⁺ (CD8tg⁺) cells have equivalent levels of T cell receptor expression as CD8end⁺ cells, respond to cognate antigen and, upon stimulation, they exhibit a phenotype characteristic of CD4⁺ helper T cells. These data are consistent with a model of differentiation that predicts that thymocytes become functionally committed to a helper or cytotoxic lineage before the final step of positive selection and independently of MHC specificity of their T cell receptor.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/1074-7613(94)90078-7DOIArticle
ORCID:
AuthorORCID
Baltimore, David0000-0001-8723-8190
Additional Information:© 1994 by Cell Press. Received 28 February 1994, Revised 1 June 1994. The authors wish to thank Mrs. M. Burke for expert secretarial assistance, Ms. T. Norton for excellent animal husbandry, and Mr. J. Brock for graphics work. Ors. A. Mellor, B. Stockinger, R. Zamoyska, and G. Klaus (National Institute for Medical Research, London) for scientific discussions and reagents. Ors. D. Gray (Royal Postgraduate Medical School, Hammersmith, London) and R. Noelle (Dartmouth Medical School, New Hampshire) for MAbs. P. C. and D. M. were supported by grants from the European Community.
Funders:
Funding AgencyGrant Number
European CommunityUNSPECIFIED
Issue or Number:4
Record Number:CaltechAUTHORS:20200513-080630337
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200513-080630337
Official Citation:Paola Corbella, Demetrius Moskophidis, Eugenia Spanopoulou, Clio Mamalaki, Mauro Tolaini, Andrea Itano, Deborah Lans, David Baltimore, Ellen Robeyj, Dimitris Kioussis, Functional commitment to helper T cell lineage precedes positive selection and is independent of T cell receptor MHC specificity, Immunity, Volume 1, Issue 4, 1994, Pages 269-276, ISSN 1074-7613, https://doi.org/10.1016/1074-7613(94)90078-7. (http://www.sciencedirect.com/science/article/pii/1074761394900787)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103166
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:13 May 2020 15:18
Last Modified:13 May 2020 15:18

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