Mycolic acid-specific T Cells protect against Mycobacterium Tuberculosis infection in a humanized transgenic mouse model
- Northwestern University, United States
Abstract
Group 1 CD1 molecules, CD1a, CD1b and CD1c, present lipid antigens from Mycobacterium tuberculosis (Mtb) to T cells. Mtb lipid-specific group 1 CD1-restricted T cells have been detected in Mtb-infected individuals. However, their role in protective immunity against Mtb remains unclear due to the absence of group 1 CD1 expression in mice. To overcome the challenge, we generated mice that expressed human group 1 CD1 molecules (hCD1Tg) and a CD1b-restricted, mycolic-acid specific TCR (DN1Tg). Using DN1Tg/hCD1Tg mice, we found that activation of DN1 T cells was initiated in the mediastinal lymph nodes and showed faster kinetics compared to Mtb Ag85B-specific CD4+ T cells after aerosol infection with Mtb. Additionally, activated DN1 T cells exhibited polyfunctional characteristics, accumulated in lung granulomas, and protected against Mtb infection. Therefore, our findings highlight the vaccination potential of targeting group 1 CD1-restricted lipid-specific T cells against Mtb infection.
Article and author information
Author details
Reviewing Editor
- Marco Colonna, Washington University School of Medicine, United States
Ethics
Animal experimentation: This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Animal Care and Use Committee of the Northwestern University (Protocol number: 2012-1736).
Version history
- Received: May 4, 2015
- Accepted: November 1, 2015
- Accepted Manuscript published: December 10, 2015 (version 1)
- Version of Record published: January 5, 2016 (version 2)
Copyright
© 2015, Zhao et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Mycolic acid-specific T Cells protect against Mycobacterium Tuberculosis infection in a humanized transgenic mouse model
eLife 4:e08525.
https://doi.org/10.7554/eLife.08525
