Thymic selection in CD8 transgenic mice supports an instructive model for commitment to a CD4 or CD8 lineage.
Immature thymocytes, which coexpress CD4 and CD8, give rise to mature CD4+CD8- and CD4-CD8+ T cells. Only those T cells that recognize self-MHC are selected to mature, a process known as positive selection. The specificity of the T cell antigen receptor (TCR) for class I or class II MHC influences the commitment to a CD4 or CD8 lineage. This may occur by a directed mechanism or by stochastic commitment followed by a selection step that allows only CD8+, class I-specific and CD4+, class II-specific cells to survive. We have generated a mouse line expressing a CD8 transgene under the control of the T cell-specific CD2 regulatory sequences. Although constitutive CD8 expression does not affect thymic selection of CD4+ cells, selection of a class I-specific TCR in the CD8 subset is substantially improved. This outcome is consistent with a model for positive selection in which selection occurs at a developmental stage in which both CD4 and CD8 are expressed, and positive selection by class I MHC generates an instructive signal that directs differentiation to a CD8 lineage.
Robey
E A
EA
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032.
Fowlkes
B J
BJ
Gordon
J W
JW
Kioussis
D
D
von Boehmer
H
H
Ramsdell
F
F
Axel
R
R
D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D015704:CD4 Antigens / Q000235:genetics* / Q000276:immunology; D016827:CD8 Antigens; D005434:Flow Cytometry; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D013269:Stochastic Processes; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens