Enhanced T cell maturation and altered lineage commitment in T cell receptor/CD4-transgenic mice.
The two mature subsets of T lymphocytes, CD4+ and CD8+ cells arise from a common progenitor during development in the thymus. The differentiation of this progenitor cell into one of the two mature T cell subsets is determined by the specificity of the alpha beta TCR for MHC class I or class II molecules. Using a line of TCR-transgenic mice expressing an MHC class II-specific TCR, 2B4, we have examined the thymocyte subsets present in a selecting versus a nonselecting MHC background. Our results are consistent with the model that CD4 versus CD8 downregulation occurs stochastically. In an effort to confirm these findings, we examined T cell development in double-transgenic mice expressing high levels of a CD4-transgene plus the 2B4 TCR transgenes. Unlike the findings with MHC class I-specific TCR-transgenic models, peripheral T cells in these mice include a substantial fraction of MHC class II-specific (2B4+) T cells expressing CD8 plus the transgene-encoded CD4. In addition, analysis of both thymocytes and peripheral T cells in these double-transgenic mice indicate that CD4 overexpression also leads to a striking enhancement of T cell maturation in 2B4 TCR-transgenic mice. Together with the studies of others, these data support a stochastic model for CD4 versus CD8 lineage commitment of an MHC class II-specific TCR during T cell development in the thymus.
Lieberman
S A
SA
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Spain
L M
LM
Wang
L
L
Berg
L J
LJ
D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000096:biosynthesis / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics*; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology
D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)