title: CD1-restricted adaptive immune responses to Mycobacteria in human group 1 CD1 transgenic mice.
abstract: Group 1 CD1 (CD1a, CD1b, and CD1c)-restricted T cells recognize mycobacterial lipid antigens and are found at higher frequencies in Mycobacterium tuberculosis (Mtb)-infected individuals. However, their role and dynamics during infection remain unknown because of the lack of a suitable small animal model. We have generated human group 1 CD1 transgenic (hCD1Tg) mice that express all three human group 1 CD1 isoforms and support the development of group 1 CD1-restricted T cells with diverse T cell receptor usage. Both mycobacterial infection and immunization with Mtb lipids elicit group 1 CD1-restricted Mtb lipid-specific T cell responses in hCD1Tg mice. In contrast to CD1d-restricted NKT cells, which rapidly respond to initial stimulation but exhibit anergy upon reexposure, group 1 CD1-restricted T cells exhibit delayed primary responses and more rapid secondary responses, similar to conventional T cells. Collectively, our data demonstrate that group 1 CD1-restricted T cells participate in adaptive immune responses upon mycobacterial infection and could serve as targets for the development of novel Mtb vaccines.
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Kyrie
authors.initials: K
authors.lastname: Felio
authors.forename: Hanh
authors.initials: H
authors.lastname: Nguyen
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Dascher
authors.forename: Hak-Jong
authors.initials: HJ
authors.lastname: Choi
authors.forename: Sha
authors.initials: S
authors.lastname: Li
authors.forename: Michael I
authors.initials: MI
authors.lastname: Zimmer
authors.forename: Angela
authors.initials: A
authors.lastname: Colmone
authors.forename: D Branch
authors.initials: DB
authors.lastname: Moody
authors.forename: Michael B
authors.initials: MB
authors.lastname: Brenner
authors.forename: Chyung-Ru
authors.initials: CR
authors.lastname: Wang
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018949:Antigens, CD1 / Q000276:immunology*; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D000939:Epitopes; D006801:Humans; D007109:Immunity / Q000276:immunology*; D007114:Immunization; D007700:Kinetics; D008055:Lipids / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D018716:Molecular Mimicry; D009161:Mycobacterium / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
chemical_list: D018949:Antigens, CD1; D000939:Epitopes; D008055:Lipids