IL-2 Restores T-Cell Dysfunction Induced by Persistent Mycobacterium tuberculosis Antigen Stimulation
Tuberculosis (TB) is a chronic disease mainly caused by Mycobacterium tuberculosis. The function of T cells usually decreased and even exhausted in severe TB such as multiple drug resistant TB (MDR-TB), which might lead to the failure of treatment in return. The mechanism of T cell dysfunction in TB...
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Frontiers Media S.A.
2019-10-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02350/full |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xun Liu Xun Liu Fei Li Fei Li Hongxia Niu Hongxia Niu Lan Ma Lan Ma Jianzhu Chen Ying Zhang Liang Peng Chao Gan Chao Gan Xingming Ma Bingdong Zhu Bingdong Zhu |
spellingShingle |
Xun Liu Xun Liu Fei Li Fei Li Hongxia Niu Hongxia Niu Lan Ma Lan Ma Jianzhu Chen Ying Zhang Liang Peng Chao Gan Chao Gan Xingming Ma Bingdong Zhu Bingdong Zhu IL-2 Restores T-Cell Dysfunction Induced by Persistent Mycobacterium tuberculosis Antigen Stimulation Frontiers in Immunology Mycobacterium tuberculosis T cell exhaustion T cell dysfunction antigen persistence IL-2 |
author_facet |
Xun Liu Xun Liu Fei Li Fei Li Hongxia Niu Hongxia Niu Lan Ma Lan Ma Jianzhu Chen Ying Zhang Liang Peng Chao Gan Chao Gan Xingming Ma Bingdong Zhu Bingdong Zhu |
author_sort |
Xun Liu |
title |
IL-2 Restores T-Cell Dysfunction Induced by Persistent Mycobacterium tuberculosis Antigen Stimulation |
title_short |
IL-2 Restores T-Cell Dysfunction Induced by Persistent Mycobacterium tuberculosis Antigen Stimulation |
title_full |
IL-2 Restores T-Cell Dysfunction Induced by Persistent Mycobacterium tuberculosis Antigen Stimulation |
title_fullStr |
IL-2 Restores T-Cell Dysfunction Induced by Persistent Mycobacterium tuberculosis Antigen Stimulation |
title_full_unstemmed |
IL-2 Restores T-Cell Dysfunction Induced by Persistent Mycobacterium tuberculosis Antigen Stimulation |
title_sort |
il-2 restores t-cell dysfunction induced by persistent mycobacterium tuberculosis antigen stimulation |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-10-01 |
description |
Tuberculosis (TB) is a chronic disease mainly caused by Mycobacterium tuberculosis. The function of T cells usually decreased and even exhausted in severe TB such as multiple drug resistant TB (MDR-TB), which might lead to the failure of treatment in return. The mechanism of T cell dysfunction in TB is still not clear. In this study we set up a mouse model of T cell dysfunction by persistent M. tuberculosis antigen stimulation and investigated the therapeutic role of interleukin 2 (IL-2) in it. C57BL/6 mice were primed with Mycobacterium bovis Bacillus Calmette-Guérin (BCG) and boosted repeatedly with a combination of M. tuberculosis fusion proteins Mtb10.4-HspX (MH) plus ESAT6-Ag85B-MPT64 <190−198>-Mtb8.4-Rv2626c (LT70) or MH plus ESAT6 and CFP10 with adjuvant of N, N′-dimethyl-N, N′-dioctadecylammonium bromide (DDA) plus polyinosinic-polycytidylic acid (Poly I:C). Following persistent antigen stimulation, the mice were treated with IL-2 and the therapeutic effects were analyzed. The results showed that compared with the mice that received transient antigen stimulation (boost twice), persistent antigen stimulation (boost more than 10 times) resulted in decrease of antigen specific IFN-γ and IL-2 production, reduction of memory CD8+ T cells, over-expression of immune checkpoint programmed cell death protein 1 (PD-1), and impaired the protective immunity against bacterial challenge. Treating the T cell functionally exhausted mice with IL-2 restored antigen-specific T cell responses and protective efficacy. In conclusion, persistent stimulation with M. tuberculosis antigens induced T cell dysfunction, which could be restored by complement of IL-2. |
topic |
Mycobacterium tuberculosis T cell exhaustion T cell dysfunction antigen persistence IL-2 |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.02350/full |
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doaj-0ee02fdf47d3489185d448d69ca1a76b2020-11-25T03:25:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-10-011010.3389/fimmu.2019.02350450697IL-2 Restores T-Cell Dysfunction Induced by Persistent Mycobacterium tuberculosis Antigen StimulationXun Liu0Xun Liu1Fei Li2Fei Li3Hongxia Niu4Hongxia Niu5Lan Ma6Lan Ma7Jianzhu Chen8Ying Zhang9Liang Peng10Chao Gan11Chao Gan12Xingming Ma13Bingdong Zhu14Bingdong Zhu15Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation and Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaSchool of Basic Medical Sciences, Institute of Pathogen Biology, Lanzhou University, Lanzhou, ChinaGansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation and Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaSchool of Basic Medical Sciences, Institute of Pathogen Biology, Lanzhou University, Lanzhou, ChinaGansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation and Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaSchool of Basic Medical Sciences, Institute of Pathogen Biology, Lanzhou University, Lanzhou, ChinaGansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation and Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaSchool of Basic Medical Sciences, Institute of Pathogen Biology, Lanzhou University, Lanzhou, ChinaDepartment of Biology, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United StatesDepartment of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United StatesCenter of Life Science, School of Life Sciences, Lanzhou University, Lanzhou, ChinaGansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation and Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaSchool of Basic Medical Sciences, Institute of Pathogen Biology, Lanzhou University, Lanzhou, ChinaGansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation and Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaGansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation and Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaSchool of Basic Medical Sciences, Institute of Pathogen Biology, Lanzhou University, Lanzhou, ChinaTuberculosis (TB) is a chronic disease mainly caused by Mycobacterium tuberculosis. The function of T cells usually decreased and even exhausted in severe TB such as multiple drug resistant TB (MDR-TB), which might lead to the failure of treatment in return. The mechanism of T cell dysfunction in TB is still not clear. In this study we set up a mouse model of T cell dysfunction by persistent M. tuberculosis antigen stimulation and investigated the therapeutic role of interleukin 2 (IL-2) in it. C57BL/6 mice were primed with Mycobacterium bovis Bacillus Calmette-Guérin (BCG) and boosted repeatedly with a combination of M. tuberculosis fusion proteins Mtb10.4-HspX (MH) plus ESAT6-Ag85B-MPT64 <190−198>-Mtb8.4-Rv2626c (LT70) or MH plus ESAT6 and CFP10 with adjuvant of N, N′-dimethyl-N, N′-dioctadecylammonium bromide (DDA) plus polyinosinic-polycytidylic acid (Poly I:C). Following persistent antigen stimulation, the mice were treated with IL-2 and the therapeutic effects were analyzed. The results showed that compared with the mice that received transient antigen stimulation (boost twice), persistent antigen stimulation (boost more than 10 times) resulted in decrease of antigen specific IFN-γ and IL-2 production, reduction of memory CD8+ T cells, over-expression of immune checkpoint programmed cell death protein 1 (PD-1), and impaired the protective immunity against bacterial challenge. Treating the T cell functionally exhausted mice with IL-2 restored antigen-specific T cell responses and protective efficacy. In conclusion, persistent stimulation with M. tuberculosis antigens induced T cell dysfunction, which could be restored by complement of IL-2.https://www.frontiersin.org/article/10.3389/fimmu.2019.02350/fullMycobacterium tuberculosisT cell exhaustionT cell dysfunctionantigen persistenceIL-2 |