title: The generation of mature, single-positive thymocytes in vivo is dysregulated by CD69 blockade or overexpression.
abstract: During development in the thymus, mature CD4+ or CD8+ cells are derived from immature CD4+CD8+ cells through a series of selection events. One of the hallmarks of this maturation process is the expression of CD69, which first appears on thymocytes as they begin positive selection. We have used blockade and overexpression of CD69 to determine the role of CD69 in thymocyte development. Blockade of CD69 led to a reduction in single-positive cells and a concomitant increase in double-positive cells in the thymus. Overexpression of a CD69 transgene in the thymus resulted in a dramatic increase in both CD8SP and CD4SP cells. Coexpression with a TCR transgene demonstrated that both positive and negative selection were enhanced by the increased levels of CD69 on thymocytes. Finally, mice overexpressing CD69 displayed a sharp reduction in the number of T cells in the spleen and lymph node. Taken as a whole, these data suggest the involvement of CD69 in the process of selection and maturation during the trafficking of thymocytes to the medulla.
authors.affiliation: Department of Molecular Immunology, Graduate School of Medicine, Chiba University, Inohana, Chiba, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Kasprowicz
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Yamashita
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Schubert
authors.forename: Geoffery
authors.initials: G
authors.lastname: Gillard
authors.forename: Motoko
authors.initials: M
authors.lastname: Kimura
authors.forename: Arnaud
authors.initials: A
authors.lastname: Didierlaurent
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.forename: Steven F
authors.initials: SF
authors.lastname: Ziegler
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019070:Cell Lineage; D005434:Flow Cytometry; D016130:Immunophenotyping; D037181:Lectins, C-Type; D008198:Lymph Nodes / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017384:Sequence Deletion; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000276:immunology*; D013950:Thymus Gland / Q000254:growth & development / Q000276:immunology*; D000099192:CD69 Antigens
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D000099192:CD69 Antigens