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

Paola Corbella, Demetrius Moskophidis, Eugenia Spanopoulou, Clio Mamalaki, Mauro Tolaini, Andrea Itano, Deborah Lans, David Baltimore, Ellen Robeyj, Dimitris Kioussis

Research output: Contribution to journalArticle

71 Scopus citations

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-I-) 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.

Original languageEnglish (US)
Pages (from-to)269-276
Number of pages8
JournalImmunity
Volume1
Issue number4
DOIs
StatePublished - Jul 1994
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Corbella, P., Moskophidis, D., Spanopoulou, E., Mamalaki, C., Tolaini, M., Itano, A., Lans, D., Baltimore, D., Robeyj, E., & Kioussis, D. (1994). Functional commitment to helper T cell lineage precedes positive selection and is independent of T cell receptor MHC specificity. Immunity, 1(4), 269-276. https://doi.org/10.1016/1074-7613(94)90078-7