title: Positive selecting cell type determines the phenotype of MHC class Ib-restricted CD8+ T cells.
abstract: Several studies have demonstrated an apparent link between positive selection on hematopoietic cells (HCs) and an "innate" T-cell phenotype. Whereas conventional CD8(+) T cells are primarily selected on thymic epithelial cells (TECs) and certain innate T cells are exclusively selected on HCs, MHC class Ib-restricted CD8(+) T cells appear to be selected on both TECs and HCs. However, whether TEC- and HC-selected T cells represent distinct lineages or whether the same T-cell precursors have the capacity to be selected on either cell type is unknown. Using an M3-restricted T-cell receptor transgenic mouse model, we demonstrate that not only are MHC class Ib-restricted CD8(+) T cells capable of being selected on either cell type but that selecting cell type directly affects the phenotype of the resulting CD8(+) T cells. M3-restricted CD8(+) T cells selected on HCs acquire a more activated phenotype and possess more potent effector functions than those selected on TECs. Additionally, these two developmental pathways are active in the generation of the natural pool of M3-restricted CD8(+) T cells. Our results suggest that these two distinct populations may allow MHC class Ib-restricted CD8(+) T cells to occupy different immunological niches playing unique roles in immune responses to infection.
authors.affiliation: Department of Microbiology and Immunology, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Hoonsik
authors.initials: H
authors.lastname: Cho
authors.forename: Yaw
authors.initials: Y
authors.lastname: Bediako
authors.forename: Honglin
authors.initials: H
authors.lastname: Xu
authors.forename: Hak-Jong
authors.initials: HJ
authors.lastname: Choi
authors.forename: Chyung-Ru
authors.initials: CR
authors.lastname: Wang
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors