IL-2 Restores T-Cell Dysfunction Induced by Persistent Mycobacterium tuberculosis Antigen Stimulation
Authors: Xingming Ma
Liang Peng
Xun Liu
Jianzhu Chen
Fei Li
Bingdong Zhu
Ying Zhang
Chao Gan
Hongxia Niu
Lan Ma
Journal: Frontiers in Immunology (2019)
Discipline: IMMUNOLOGY
Keywords: IL-2; Mycobacterium tuberculosis; T cell dysfunction; T cell exhaustion; antigen persistence.
Affiliations: Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation and Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China., School of Basic Medical Sciences, Institute of Pathogen Biology, Lanzhou University, Lanzhou, China., Department of Biology, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States., Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States., Center of Life Science, School of Life Sciences, Lanzhou University, Lanzhou, China.

Abstract:  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 &lt;190-198&gt;-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. 

Retracted: No

PubPeer comments:
 A Corrigendum on IL-2 Restores T-Cell Dysfunction Induced by Persistent Mycobacterium tuberculosis Antigen Stimulation by Liu, X., Li, F., Niu, H., Ma, L., Chen, J., Zhang, Y., et al. (2019). Front. Immunol. 10:2350. doi: 10.3389 fimmu.2019.02350 In the original article, there was a mistake in Figure 3 as published. In Figure 3A some panels were accidentally duplicated. The corrected Figure 3 appears below. ![file] , 
 This paper is one of a small collection of papers which appears to include a typographical error in the spelling of an manufacturer. The company name is ACEA Biosciences headquartered in San Diego. In this paper and the others, the name is spelled ACEC. This suggests that the paper was written from a common template, although the author groups are mostly different. *** ![file] ,