title: Positive selection of thymocytes induced by gene transfer: MHC class II-mediated selection of CD8 lineage cells.
abstract: Recombinant adenovirus vectors are powerful tools for inducing de novo gene expression in vivo. Here we have exploited them to study the specificity of CD4/CD8 lineage commitment during thymocyte positive selection, transferring MHC class II genes directly into thymi of mice deficient in both class I and II molecules. Expression of class II molecules was induced on cortical stroma, provoking the selection of a large population of mature CD4(+)CD8(-) cells, as expected, but also of a significant number of CD4(-)CD8(+) cells. The latter constituted a diverse population, containing both immature precursors and, though less frequent, cells that were mature according to several criteria. CD4(-)CD8(+) cells appeared with the same kinetics as their CD4(+)CD8(-) counterparts, but tended to be more prevalent at early times or when thymocyte reconstitution was only modest. These observations, derived from a dynamic selection system, indicate that CD4/CD8 lineage commitment is not irredeemably linked to the class of MHC molecule driving positive selection, a conclusion most compatible with selective models of commitment.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS/INSERM/ULP), 67404 Illkirch, CU de Strasbourg, France.
authors.forename: R
authors.initials: R
authors.lastname: Rooke
authors.forename: C
authors.initials: C
authors.lastname: Waltzinger
authors.forename: C
authors.initials: C
authors.lastname: Benoist
authors.forename: D
authors.initials: D
authors.lastname: Mathis
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D016827:CD8 Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D005802:Genes, MHC Class II / Q000235:genetics*; D005822:Genetic Vectors / Q000008:administration & dosage; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D013047:Specific Pathogen-Free Organisms; D013950:Thymus Gland / Q000166:cytology* / Q000821:virology; D013997:Time Factors; D001613:beta 2-Microglobulin / Q000172:deficiency
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D001613:beta 2-Microglobulin