Functional commitment to helper T cell lineage precedes positive selection and is independent of T cell receptor MHC specificity.
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.
Corbella
P
P
Laboratory of Molecular Immunology, National Institute for Medical Research, London, England.
Moskophidis
D
D
Spanopoulou
E
E
Mamalaki
C
C
Tolaini
M
M
Itano
A
A
Lans
D
D
Baltimore
D
D
Robey
E
E
Kioussis
D
D
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers / Q000235:genetics; D005805:Genes, MHC Class I; D018398:Homeodomain Proteins; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*
D017931:DNA Primers; D018398:Homeodomain Proteins; D010455:Peptides; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; C064658:RAG-1 protein; D015847:Interleukin-4