Thymic selection in CD8 transgenic mice supports an instructive model for commitment to a CD4 or CD8 lineage

• Published in: Cell Vol. 64; no. 1; p. 99
• Main Authors: Robey, E A, Fowlkes, B J, Gordon, J W, Kioussis, D, von Boehmer, H, Ramsdell, F, Axel, R
• Format: Journal Article
• Language: English
• Published: United States 11-01-1991
• Subjects: Animals; Antigens, CD - genetics; Antigens, CD - immunology; Antigens, Differentiation, T-Lymphocyte - genetics; Antigens, Differentiation, T-Lymphocyte - immunology; CD4 Antigens - genetics; CD4 Antigens - immunology; CD8 Antigens; Flow Cytometry; Humans; Lymph Nodes - immunology; Mice; Mice, Transgenic; Models, Biological; Stochastic Processes; T-Lymphocytes - immunology; Thymus Gland - immunology
• ISSN: 0092-8674
• DOI: 10.1016/0092-8674(91)90212-H

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.