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Updated: Aug 9, 2026

Protective Efficacy and Pulmonary Immune Response Following Subcutaneous and Intranasal BCG Administration in Mice
Published on: September 19, 2016
Cutting edge: major CD8 T cell response to live bacillus Calmette-Guérin is mediated by CD1 molecules
Tetsuo Kawashima1, Yoshihiko Norose, Yoshiyuki Watanabe
1Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan.
Insights
CD8(+) T cells recognize mycobacteria via CD1 molecules, independent of MHC. These lipid-reactive T cells detect live bacillus Calmette-Guérin (BCG) and produce IFN-gamma, aiding host defense against mycobacterial infections.
Area of Science:
- Immunology
- Microbiology
- Infectious Disease
Background:
- CD8(+) T cells are vital for defense against mycobacteria in mice, but human responses are challenging to identify.
- Human group 1 CD1 molecules present mycobacterial lipids to CD8(+) T cells independently of MHC.
- CD1 molecules' location in the endocytic system aids in monitoring phagosome-resident mycobacteria.
Purpose of the Study:
- To investigate the role of CD1-restricted CD8(+) T cells in human immune responses to mycobacterial infection.
- To determine if CD1-dependent CD8(+) T cells can recognize bacillus Calmette-Guérin (BCG) in humans.
Main Methods:
- Analysis of circulating CD8(+) T cells from BCG-immunized subjects.
- Assessment of T cell recognition of BCG-infected dendritic cells (DCs).
- Evaluation of CD1 and MHC dependency of T cell responses.
- Measurement of IFN-gamma production by T cells.
Main Results:
- A significant pool of circulating CD8(+) T cells recognizing BCG-infected DCs was found in BCG-immunized individuals.
- This recognition was CD1-dependent and MHC-independent.
- These CD1-restricted T cells preferentially detected live BCG and produced IFN-gamma.
Conclusions:
- Lipid-reactive CD8(+) T cells, restricted by CD1 molecules, represent a significant component of the human immune response to mycobacteria.
- These T cells contribute to host defense by detecting live mycobacteria and producing protective cytokines like IFN-gamma.
Abstract:
MHC class I-restricted CD8(+) T cells are a crucial component of the host defense against mycobacterial infection in mice, but it has often proved very difficult to identify the CD8 T cell response in humans. Human group 1 CD1 molecules (CD1a, -b, -c) mediate MHC-independent presentation of mycobacteria-derived lipid and glycolipid Ags to CD8(+) T cells, and their intracellular localization to the endocytic system may favor efficient monitoring of phagosome-resident mycobacteria. Here, we show that bacillus Calmette-Guérin (BCG)-immunized subjects contain a significant circulating pool of CD8(+) T cells that recognize BCG-infected DCs in a CD1-dependent, but MHC-independent, manner. These CD1-restricted T cells efficiently detected live, rather than dead, BCG and produced IFN-gamma, an important cytokine for protection against mycobacterial infection. These results emphasize that lipid-reactive CD8(+) T cells may contribute to host defense against mycobacterial infection.
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