Reviews

Research progress in T cell exhaustion and its relationship with respiratory diseases

  • Ziqi DING ,
  • Qian. ZHANG
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  • Department of Respiratory and Critical Care Medicine,Affiliated Changzhou Second People′s Hospital of Nanjing Medical University,Changzhou 213164,China

Received date: 2023-12-28

  Online published: 2024-07-09

Abstract

T cell exhaustion occurs mostly in chronic infections, cancers and autoimmune diseases. Continuous antigenic stimulation leads to the generation of exhausted T cells, which is characterized by progressive loss of effector function, continuous high expression of inhibitory receptors, transcription and epigenetic changes, and metabolic disorders. The in-depth study of the specific mechanism of T cell exhaustion is providing new ideas for the immunotherapy of chronic infection, lung cancer and chronic airway inflammatory disease in respiratory diseases. This paper discussed the influencing factors and characteristics of T cell exhaustion and reviewed the current research status of T cell exhaustion and respiratory diseases.

Cite this article

Ziqi DING , Qian. ZHANG . Research progress in T cell exhaustion and its relationship with respiratory diseases[J]. The Journal of Practical Medicine, 2024 , 40(13) : 1895 -1900 . DOI: 10.3969/j.issn.1006-5725.2024.13.023

References

1 GALLIMORE A, GLITHERO A, GODKIN A, et al. Induction and exhaustion of lymphocytic choriomeningitis virus-specific cytotoxic T lymphocytes visualized using soluble tetrameric major histocompatibility complex class I-peptide complexes[J]. J Exp Med, 1998,187(9):1383-1393. doi:10.1084/jem.187.9.1383
2 SHIN M S, PARK H J, YOUNG J, et al. Implication of IL-7 receptor alpha chain expression by CD8+ T cells and its signature in defining biomarkers in aging[J]. Immun Ageing, 2022,19(1):1-8. doi:10.1186/s12979-022-00324-6
3 WHERRY E J. T cell exhaustion[J]. Nat Immunol, 2011, 12(6):492-499. doi:10.1038/ni.2035
4 LENG A, SHAH M, AHMAD S A, et al. Pathogenesis underlying neurological manifestations of long COVID syndrome and potential therapeutics[J]. Cells, 2023,12(5):816. doi:10.3390/cells12050816
5 OSUCH S, LASKUS T, PERLEJEWSKI K, et al. CD8+ T-cell exhaustion phenotype in chronic hepatitis c virus infection is associated with epitope sequence variation[J]. Front Immunol, 2022,13:903. doi:10.3389/fimmu.2022.832206
6 MISHRA K, SINGH M, SARASWAT D, et al. Dysfunctional state of T cells or exhaustion during chronic viral infections and COVID-19: A review[J]. Viral Immunol, 2022,35(4):284-290. doi:10.1089/vim.2022.0002
7 GAO Z, FENG Y, XU J, et al. T-cell exhaustion in immune-mediated inflammatory diseases: New implications for immunotherapy[J]. Front Immunol, 2022,13:977394. doi:10.3389/fimmu.2022.977394
8 DOLINA J S, BRAECKEL-BUDIMIR N V, THOMAS G D, et al. CD8+ T cell exhaustion in cancer[J]. Front Immunol, 2021,12:715234. doi:10.3389/fimmu.2021.715234
9 BARNOVA M, BOBCAKOVA A, URDOVA V, et al. Inhibitory immune checkpoint molecules and exhaustion of T cells in COVID-19[J]. Physiol Res, 2021,70(S2):S227-S247.
10 QUIGLEY M, PEREYRA F, NILSSON B, et al.Transcriptional analysis of HIV-specific CD8+ T cells shows that PD-1 inhibits T cell function by upregulating BATF[J]. Nat Med,2010,16(10):1147-1151. doi:10.1038/nm.2232
11 HAN Y, LIU D, LI L. PD-1/PD-L1 pathway: current researches in cancer[J]. Am J Cancer Res, 2020,10(3):727-742.
12 BROOKS D G, TRIFILO M J, EDELMANN K H, et al. Interleukin-10 determines viral clearance or persistence in vivo[J]. Nat Med, 2006,12(11):1301-1309. doi:10.1038/nm1492
13 HASHIMOTO M, ARAKI K, CARDENAS M A, et al. PD-1 combination therapy with IL-2 modifies CD8+ T cell exhaustion program[J]. Nature, 2022,610(7930):173-181. doi:10.1038/s41586-022-05257-0
14 HU Y, HUDSON W H, KISSICK H T, et al. TGF-beta regulates the stem-like state of PD-1+ TCF-1+ virus-specific CD8 T cells during chronic infection[J]. J Exp Med, 2022,219(10) :e20211574. doi:10.1084/jem.20211574
15 ELSAESSER H, SAUER K, BROOKS D G. IL-21 is required to control chronic viral infection[J]. Science, 2009, 324(5934):1569-1572. doi:10.1126/science.1174182
16 CUI C, WANG J, FAGERBERG E, et al. Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses[J]. Cell,2021,184(25):6101-6118. doi:10.1016/j.cell.2021.11.007
17 REN H M, LUKACHER A E, RAHMAN Z S M, et al. New developments implicating IL-21 in autoimmune disease[J]. J Autoimmun,2021,122:102689. doi:10.1016/j.jaut.2021.102689
18 ELAHI S, SHAHBAZ S, HOUSTON S. Selective upregulation of CTLA-4 on CD8+ T cells restricted by HLA-B* 35Px renders them to an exhausted phenotype in HIV-1 infection[J]. PLoS Pathog, 2020,16(8):e1008696. doi:10.1371/journal.ppat.1008696
19 OYEWOLE-SAID D, KONDURI V, VAZQUEZ-PEREZ J, et al. Beyond T-cells: functional characterization of CTLA-4 expression in immune and non-immune cell types[J]. Front Immunol, 2020,11:608024. doi:10.3389/fimmu.2020.608024
20 CHOCARRO L, BLANCO E, ZUAZO M, et al. Understanding LAG-3 signaling[J]. Int J Mol Sci, 2021,22(10):5282. doi:10.3390/ijms22105282
21 HAN J, WAN M, MA Z, et al. The TOX subfamily: all-round players in the immune system[J]. Clin Exp Immunol, 2022,208(3):268-280. doi:10.1093/cei/uxac037
22 SEN D R, KAMINSKI J, BARNITZ R A, et al. The epigenetic landscape of T cell exhaustion[J]. Science, 2016, 354(6316):1165-1169. doi:10.1126/science.aae0491
23 刘勋. 结核抗原持续刺激致T细胞耗竭实验研究及亚单位疫苗LT70-DPC的研发[D]. 兰州:兰州大学, 2016.
24 PHILLIPS B L, MEHRA S, AHSAN M H, et al. LAG3 expression in active mycobacterium tuberculosis infections[J]. Am J Pathol, 2015,185(3):820-833. doi:10.1016/j.ajpath.2014.11.003
25 SHEN L, GAO Y, LIU Y, et al. PD-1/PD-L pathway inhibits M.tb-specific CD4+ T-cell functions and phagocytosis of macrophages in active tuberculosis[J]. Sci Rep, 2016,6:38362. doi:10.1038/srep38362
26 JAYARAMAN P, JACQUES M K, ZHU C, et al. TIM3 mediates T cell exhaustion during mycobacterium tuberculosis infection[J]. PLoS Pathog, 2016,12(3):e1005490. doi:10.1371/journal.ppat.1005490
27 LOMBARDI A, VILLA S, CASTELLI V, et al. T-Cell Exhaustion in Mycobacterium tuberculosis and Nontuberculous Mycobacteria Infection: Pathophysiology and Therapeutic Perspectives[J]. Microorganisms, 2021,9(12):2460. doi:10.3390/microorganisms9122460
28 LIU X, LI F, NIU H, et al. IL-2 Restores T-Cell Dysfunction Induced by Persistent Mycobacterium tuberculosis Antigen Stimulation[J]. Front Immunol, 2019, 10:2350. doi:10.3389/fimmu.2019.02350
29 RHA M S, SHIN E C. Activation or exhaustion of CD8+ T cells in patients with COVID-19[J]. Cell Mol Immunol, 2021,18(10):2325-2333. doi:10.1038/s41423-021-00750-4
30 LIU L, WANG A, LIU X, et al. Blocking TIGIT/CD155 signalling reverses CD8+ T cell exhaustion and enhances the antitumor activity in cervical cancer[J]. J Transl Med, 2022,20(1):1-13. doi:10.1186/s12967-022-03480-x
31 SIEGEL R L, MILLER K D, WAGLE N S, et al. Cancer statistics, 2023[J]. CA Cancer J Clin, 2023,73(1):17-48. doi:10.3322/caac.21763
32 DUTTA S, GANGULY A, CHATTERJEE K, et al. Targets of immune escape mechanisms in cancer: basis for development and evolution of cancer immune checkpoint inhibitors[J]. Biology (Basel), 2023,12(2):218. doi:10.3390/biology12020218
33 CHI X, LUO S, YE P, et al. T-cell exhaustion and stemness in antitumor immunity: characteristics, mechanisms, and implications[J]. Front Immunol, 2023,14:1104771. doi:10.3389/fimmu.2023.1104771
34 CHU X, TIAN W, WANG Z, et al. Co-inhibition of TIGIT and PD-1/PD-L1 in cancer immunotherapy: mechanisms and clinical trials[J]. Mol Cancer, 2023,22(1):1-31. doi:10.1186/s12943-023-01800-3
35 SU Y, YAMAZAKI S, MORISUE R, et al. Tumor-infiltrating T cells concurrently overexpress CD200R with immune checkpoints PD-1, CTLA-4, and TIM-3 in non-small-cell lung cancer[J]. Pathobiology, 2021,88(3):218-227. doi:10.1159/000511557
36 武阳,陆翰杰,水会锋. 既往免疫经治的晚期非小细胞肺癌患者接受安罗替尼联合PD?1单抗的疗效及安全性[J]. 实用医学杂志, 2023,39(5):572-578.
37 ITAHASHI K, IRIE T, YUDA J, et al. BATF epigenetically and transcriptionally controls the activation program of regulatory T cells in human tumors[J]. Sci Immunol, 2022,7(76):eabk0957. doi:10.1126/sciimmunol.abk0957
38 ZHANG Z, LIN M, WANG J, et al. Calycosin inhibits breast cancer cell migration and invasion by suppressing EMT via BATF/TGF-β1[J]. Aging (Albany NY), 2021,13(12):16009-16023. doi:10.18632/aging.203093
39 ZHANG X, ZHANG C, QIAO M, et al. Depletion of BATF in CAR-T cells enhances antitumor activity by inducing resistance against exhaustion and formation of central memory cells[J]. Cancer Cell, 2022,40(11):1407-1422. doi:10.1016/j.ccell.2022.09.013
40 TREFNY M P, KIRCHHAMMER N, DER MAUR P AUF, et al. Deletion of SNX9 alleviates CD8 T cell exhaustion for effective cellular cancer immunotherapy[J]. Nat Commun, 2023,14(1):86. doi:10.1038/s41467-022-35583-w
41 ZHANG H, LIU S, LI Y, et al. Dysfunction of S100A4+ effector memory CD8+ T cells aggravates asthma[J]. Eur J Immunol,2022,52(6):978-993. doi:10.1002/eji.202149572
42 DIEHL S, KRAHL T, RINALDI L, et al. Inhibition of NFAT specifically in T cells prevents allergic pulmonary inflammation[J]. J Immunol, 2004,172(6):3597-3603. doi:10.4049/jimmunol.172.6.3597
43 LIN M, HUANG Z, CHEN Y, et al. Lung cancer patients with chronic obstructive pulmonary disease benefit from anti-PD-1/PD-L1 therapy[J]. Front Immunol, 2022,13:1038715. doi:10.3389/fimmu.2022.1038715
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