title: Programming for cytotoxic effector function occurs concomitantly with CD4 extinction during CD8(+) T cell differentiation in the thymus.
abstract: CD4(+) T cells are generally specialized to function as helper cells and CD8(+) T cells are generally specialized to function as cytotoxic effector cells. To explain how such concordance is achieved between co-receptor expression and immune function, we considered two possibilities. In one case, immature CD4(+)CD8(+) thymocyte precursors might first down-regulate expression of one co-receptor molecule, with the remaining co-receptor molecule subsequently activating the appropriate helper or cytotoxic functional program. Alternatively, we considered that the same intrathymic signals that selectively extinguished expression of one or the other co-receptor molecule might simultaneously initiate the appropriate helper or cytotoxic functional program. In the present study, we attempted to distinguish between these alternatives by examining thymocyte precursors of CD8(+) T cells for expression of Cathepsin C and Cathepsin W, molecules important for cytotoxic effector function. We report in developing thymocytes that Cathepsin C and Cathepsin W are expressed coordinately with extinction of CD4 co-receptor expression. We conclude that CD4 extinction and initiation of the cytotoxic functional program occurs simultaneously during differentiation of CD8(+) T cells in the thymus.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: A
authors.initials: A
authors.lastname: Bhandoola
authors.forename: B
authors.initials: B
authors.lastname: Kithiganahalli
authors.forename: L
authors.initials: L
authors.lastname: Granger
authors.forename: A
authors.initials: A
authors.lastname: Singer
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000032:analysis*; D018956:CD5 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D020789:Cathepsin C / Q000235:genetics; D056664:Cathepsin W; D002403:Cathepsins / Q000235:genetics; D002454:Cell Differentiation; D003546:Cysteine Endopeptidases / Q000235:genetics; D003602:Cytotoxicity, Immunologic; D051379:Mice; D008810:Mice, Inbred C57BL; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D018956:CD5 Antigens; D002403:Cathepsins; D020789:Cathepsin C; D056664:Cathepsin W; C534188:Ctsw protein, mouse; D003546:Cysteine Endopeptidases