Lck activity controls CD4/CD8 T cell lineage commitment.
Thymocytes carrying MHC class I-restricted TCRs differentiate into CD8 T cells, while those recognizing MHC class II become CD4 T cells. The mechanisms underlying how MHC class recognition, coreceptor expression, and effector function are coordinated are not well understood. Since the tyrosine kinase Lck binds with more affinity to CD4 than CD8, it has been proposed as a candidate to mediate this process. By using transgenic mice with altered Lck activity, we show that thymocytes carrying a class II-restricted TCR develop into functional CD8 T cells when Lck activity is reduced. Conversely, thymocytes carrying a class I-restricted TCR develop into functional CD4 T cells when Lck activity is increased. These results directly show that quantitative differences in the Lck signal control the CD4/CD8 lineage decision.
Hernández-Hoyos
G
G
Division of Biology, California Institute of Technology, Pasadena 91125, USA.
Sohn
S J
SJ
Rothenberg
E V
EV
Alberola-Ila
J
J
D000818:Animals; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D023201:CD40 Ligand; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D019070:Cell Lineage / Q000502:physiology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D019891:Leukopoiesis / Q000502:physiology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic; D013950:Thymus Gland / Q000166:cytology; D015854:Up-Regulation / Q000276:immunology
D018106:CD28 Antigens; D017252:CD3 Complex; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D023201:CD40 Ligand; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)