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Induction of Intestinal Inflammation by Adoptive Transfer of CBir1 TCR Transgenic CD4+ T Cells to Immunodeficient Mice
Published on: December 16, 2021
CD1-restricted adaptive immune responses to Mycobacteria in human group 1 CD1 transgenic mice
Kyrie Felio1, Hanh Nguyen, Christopher C Dascher
1Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Insights
Human CD1 transgenic mice reveal group 1 CD1-restricted T cells are key players in adaptive immunity against Mycobacterium tuberculosis (Mtb). These cells show delayed primary and faster secondary responses, offering new vaccine targets.
Area of Science:
- Immunology
- Microbiology
- Transgenic Animal Models
Background:
- Group 1 CD1-restricted T cells recognize mycobacterial lipid antigens.
- These cells are more frequent in individuals infected with Mycobacterium tuberculosis (Mtb).
- Their role and dynamics during infection are poorly understood due to a lack of suitable animal models.
Purpose of the Study:
- To generate and characterize a human group 1 CD1 transgenic mouse model (hCD1Tg).
- To investigate the adaptive immune responses of group 1 CD1-restricted T cells to mycobacterial antigens in vivo.
Main Methods:
- Generation of hCD1Tg mice expressing human CD1a, CD1b, and CD1c.
- Infection and immunization with Mtb lipids in hCD1Tg mice.
- Analysis of T cell receptor usage and response dynamics.
Main Results:
- hCD1Tg mice support the development of diverse group 1 CD1-restricted T cells.
- Mycobacterial infection and Mtb lipid immunization elicit specific T cell responses.
- Group 1 CD1-restricted T cells exhibit delayed primary and accelerated secondary responses, unlike CD1d-restricted NKT cells.
Conclusions:
- Group 1 CD1-restricted T cells are involved in adaptive immunity to Mtb infection.
- These T cells demonstrate distinct response kinetics compared to NKT cells.
- Group 1 CD1-restricted T cells represent potential targets for novel Mtb vaccines.
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.

