IL-2 Restores T-Cell Dysfunction Induced by Persistent Mycobacterium tuberculosis Antigen Stimulation

Tuberculosis (TB) is a chronic disease mainly caused by . 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 th...

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Bibliographic Details
Published in:Frontiers in immunology 2019-10, Vol.10, p.2350-2350
Main Authors: Liu, Xun, Li, Fei, Niu, Hongxia, Ma, Lan, Chen, Jianzhu, Zhang, Ying, Peng, Liang, Gan, Chao, Ma, Xingming, Zhu, Bingdong
Format: Article
Language:English
Subjects:
antigen persistence
IL-2
Immunology
Mycobacterium tuberculosis
T cell dysfunction
T cell exhaustion
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Summary:Tuberculosis (TB) is a chronic disease mainly caused by . 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 antigen stimulation and investigated the therapeutic role of interleukin 2 (IL-2) in it. C57BL/6 mice were primed with Bacillus Calmette-Guérin (BCG) and boosted repeatedly with a combination of fusion proteins Mtb10.4-HspX (MH) plus ESAT6-Ag85B-MPT64 -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 antigens induced T cell dysfunction, which could be restored by complement of IL-2.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2019.02350