CD1-restricted adaptive immune responses to Mycobacteria in human group 1 CD1 transgenic mice.
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.
Felio
Kyrie
K
Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Nguyen
Hanh
H
Dascher
Christopher C
CC
Choi
Hak-Jong
HJ
Li
Sha
S
Zimmer
Michael I
MI
Colmone
Angela
A
Moody
D Branch
DB
Brenner
Michael B
MB
Wang
Chyung-Ru
CR
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
D018949:Antigens, CD1; D000939:Epitopes; D008055:Lipids