title: Origin, differentiation, and repertoire selection of CD3+CD4-CD8- thymocytes bearing either alpha beta or gamma delta T cell receptors.
abstract: It has been widely accepted that CD3+CD4-CD8- T cells expressing TCR-alpha beta or TCR-gamma delta (found in the thymus as well as in the periphery) represent lineages distinct from either CD4+CD8- and CD4-CD8+ single-positive T cells expressing TCR-alpha beta. However, the origin, differentiation pathway, and TCR-repertoire selection of CD3+CD4-CD8- T cells remain controversial. We demonstrate that CD3+CD4-CD8- thymocytes can be separated into three subsets based on their expression of heat-stable Ag (HSA) and CD44. Our results further suggest the following: 1) the HSA+ subset represents a pre-selection population, although the HSA- subset is a postselection subset; 2) the high incidence of V beta 8.2 usage among CD3+CD4-CD8- thymocytes is a result of positive selection, rather than a predetermined event at a precursor cell level; 3) the maturation of CD3+CD4-CD8- thymocytes proceeds along the following differentiation pathway: HSA+CD44(-)-->HSA-CD44(-)-->HSA-CD44+. Both TCR-alpha beta +CD4-CD8- and TCR-gamma delta +CD4-CD8- thymocytes show similar differentiation processes; 4) CD3+CD4-CD8-cells directly differentiate from CD25+CD3-CD4-CD8- thymocytes which include precursor cells for both the CD3+CD4-CD8- and the CD4+CD8-/CD4-CD8+ lineages. Taken together, these results suggest that the CD25+CD3-CD4-CD8- stage of thymocyte differentiation represents a branching point for either the CD4+CD8- or CD4-CD8+ single-positive lineages or the CD3+CD4-CD8- lineages.
authors.affiliation: DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304.
authors.forename: T
authors.initials: T
authors.lastname: Suda
authors.forename: A
authors.initials: A
authors.lastname: Zlotnik
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000032:analysis*; D015704:CD4 Antigens / Q000032:analysis*; D016827:CD8 Antigens / Q000032:analysis*; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D016201:Receptors, Lymphocyte Homing / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015375:Receptors, Interleukin-2; D016201:Receptors, Lymphocyte Homing