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http://dx.doi.org/10.5483/BMBRep.2022.55.2.183

Emerging role of bystander T cell activation in autoimmune diseases  

Shim, Chae-Hyeon (Department of Life Science, College of Natural Sciences, Hanyang University)
Cho, Sookyung (Department of Life Science, College of Natural Sciences, Hanyang University)
Shin, Young-Mi (Department of Life Science, College of Natural Sciences, Hanyang University)
Choi, Je-Min (Department of Life Science, College of Natural Sciences, Hanyang University)
Publication Information
BMB Reports / v.55, no.2, 2022 , pp. 57-64 More about this Journal
Abstract
Autoimmune disease is known to be caused by unregulated self-antigen-specific T cells, causing tissue damage. Although antigen specificity is an important mechanism of the adaptive immune system, antigen non-related T cells have been found in the inflamed tissues in various conditions. Bystander T cell activation refers to the activation of T cells without antigen recognition. During an immune response to a pathogen, bystander activation of self-reactive T cells via inflammatory mediators such as cytokines can trigger autoimmune diseases. Other antigen-specific T cells can also be bystander-activated to induce innate immune response resulting in autoimmune disease pathogenesis along with self-antigen-specific T cells. In this review, we summarize previous studies investigating bystander activation of various T cell types (NKT, γδ T cells, MAIT cells, conventional CD4+, and CD8+ T cells) and discuss the role of innate-like T cell response in autoimmune diseases. In addition, we also review previous findings of bystander T cell function in infection and cancer. A better understanding of bystander-activated T cells versus antigen-stimulated T cells provides a novel insight to control autoimmune disease pathogenesis.
Keywords
Antigen specificity; Autoimmune disease; Bystander T cell activation; Innate-like functions;
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1 Reynolds JM, Martinez GJ, Chung Y and Dong C (2012) Toll-like receptor 4 signaling in T cells promotes autoimmune inflammation. Proc Natl Acad Sci U S A 109, 13064-13069   DOI
2 Nogai A, Siffrin V, Bonhagen K et al (2005) Lipopolysaccharide injection induces relapses of experimental autoimmune encephalomyelitis in nontransgenic mice via bystander activation of autoreactive CD4+ cells. J Immunol 175, 959-966   DOI
3 Sobek V, Birkner N, Falk I et al (2004) Direct Toll-like receptor 2 mediated co-stimulation of T cells in the mouse system as a basis for chronic inflammatory joint disease. Arthritis Res Ther 6, R433-446   DOI
4 Simoni Y, Gautron AS, Beaudoin L et al (2011) NOD mice contain an elevated frequency of iNKT17 cells that exacerbate diabetes. Eur J Immunol 41, 3574-3585   DOI
5 Ben-Sasson SZ, Caucheteux S, Crank M, Hu-Li J and Paul WE (2011) IL-1 acts on T cells to enhance the magnitude of in vivo immune responses. Cytokine 56, 122-125   DOI
6 Nakamura R, Maeda N, Shibata K, Yamada H, Kase T and Yoshikai Y (2010) Interleukin-15 is critical in the pathogenesis of influenza a virus-induced acute lung injury. J Virol 84, 5574-5582   DOI
7 Joncker NT, Marloie MA, Chernysheva A et al (2006) Antigen-independent accumulation of activated effector/memory T lymphocytes into human and murine tumors. Int J Cancer 118, 1205-1214   DOI
8 Ponzetta A, Carriero R, Carnevale S et al (2019) Neutrophils driving unconventional T cells mediate resistance against murine sarcomas and selected human tumors. Cell 178, 346-360.e324   DOI
9 Zhang X, Sun S, Hwang I, Tough DF and Sprent J (1998) Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15. Immunity 8, 591-599   DOI
10 Chung Y, Chang SH, Martinez GJ et al (2009) Critical regulation of early Th17 cell differentiation by interleukin-1 signaling. Immunity 30, 576-587   DOI
11 Jiang W, Younes SA, Funderburg NT et al (2014) Cycling memory CD4+ T cells in HIV disease have a diverse T cell receptor repertoire and a phenotype consistent with bystander activation. J Virol 88, 5369-5380   DOI
12 Kim J, Chang DY, Lee HW et al (2018) Innate-like cytotoxic function of bystander-activated CD8(+) T cells is associated with liver injury in acute hepatitis A. Immunity 48, 161-173.e165   DOI
13 Tough DF, Borrow P and Sprent J (1996) Induction of bystander T cell proliferation by viruses and type I interferon in vivo. Science 272, 1947-1950   DOI
14 Chakir H, Lam DK, Lemay AM and Webb JR (2003) "Bystander polarization" of CD4+ T cells: activation with high-dose IL-2 renders naive T cells responsive to IL-12 and/or IL-18 in the absence of TCR ligation. Eur J Immunol 33, 1788-1798   DOI
15 Ussher JE, Bilton M, Attwod E et al (2014) CD161++ CD8+ T cells, including the MAIT cell subset, are specifically activated by IL-12+IL-18 in a TCR-independent manner. Eur J Immunol 44, 195-203   DOI
16 Doisne JM, Soulard V, Becourt C et al (2011) Cutting edge: crucial role of IL-1 and IL-23 in the innate IL-17 response of peripheral lymph node NK1.1- invariant NKT cells to bacteria. J Immunol 186, 662-666   DOI
17 Haas JD, Gonzalez FH, Schmitz S et al (2009) CCR6 and NK1.1 distinguish between IL-17A and IFN-gamma-producing gammadelta effector T cells. Eur J Immunol 39, 3488-3497   DOI
18 Kjer-Nielsen L, Patel O, Corbett AJ et al (2012) MR1 presents microbial vitamin B metabolites to MAIT cells. Nature 491, 717-723   DOI
19 Swain SL, Hu H and Huston G (1999) Class II-independent generation of CD4 memory T cells from effectors. Science 286, 1381-1383   DOI
20 Tan LC, Mowat AG, Fazou C et al (2000) Specificity of T cells in synovial fluid: high frequencies of CD8(+) T cells that are specific for certain viral epitopes. Arthritis Res 2, 154-164   DOI
21 Terashima A, Watarai H, Inoue S et al (2008) A novel subset of mouse NKT cells bearing the IL-17 receptor B responds to IL-25 and contributes to airway hyperreactivity. J Exp Med 205, 2727-2733   DOI
22 Tietze JK, Wilkins DE, Sckisel GD et al (2012) Delineation of antigen-specific and antigen-nonspecific CD8(+) memory T-cell responses after cytokine-based cancer immunotherapy. Blood 119, 3073-3083   DOI
23 Lee YK, Landuyt AE, Lobionda S, Sittipo P, Zhao Q and Maynard CL (2017) TCR-independent functions of Th17 cells mediated by the synergistic actions of cytokines of the IL-12 and IL-1 families. PLoS One 12, e0186351   DOI
24 van Aalst S, Ludwig IS, van der Zee R, van Eden W and Broere F (2017) Bystander activation of irrelevant CD4+ T cells following antigen-specific vaccination occurs in the presence and absence of adjuvant. PLoS One 12, e0177365   DOI
25 Lu J, Giuntoli RL 2nd, Omiya R, Kobayashi H, Kennedy R and Celis E (2002) Interleukin 15 promotes antigen-independent in vitro expansion and long-term survival of antitumor cytotoxic T lymphocytes. Clin Cancer Res 8, 3877-3884
26 Crosby EJ, Goldschmidt MH, Wherry EJ and Scott P (2014) Engagement of NKG2D on bystander memory CD8 T cells promotes increased immunopathology following Leishmania major infection. PLoS Pathog 10, e1003970   DOI
27 Van Kaer L, Postoak JL, Wang C, Yang G and Wu L (2019) Innate, innate-like and adaptive lymphocytes in the pathogenesis of MS and EAE. Cell Mol Immunol 16, 531-539   DOI
28 Pane JA and Coulson BS (2015) Lessons from the mouse: potential contribution of bystander lymphocyte activation by viruses to human type 1 diabetes. Diabetologia 58, 1149-1159   DOI
29 Newman JH, Chesson CB, Herzog NL et al (2020) Intratumoral injection of the seasonal flu shot converts immunologically cold tumors to hot and serves as an immunotherapy for cancer. Proc Natl Acad Sci U S A 117, 1119-1128   DOI
30 Kobayashi M, Yasui N, Ishimaru N, Arakaki R and Hayashi Y (2004) Development of autoimmune arthritis with aging via bystander T cell activation in the mouse model of Sjogren's syndrome. Arthritis Rheum 50, 3974-3984   DOI
31 Doisne JM, Urrutia A, Lacabaratz-Porret C et al (2004) CD8+ T cells specific for EBV, cytomegalovirus, and influenza virus are activated during primary HIV infection. J Immunol 173, 2410-2418   DOI
32 Bastidas S, Graw F, Smith MZ, Kuster H, Gunthard HF and Oxenius A (2014) CD8+ T cells are activated in an antigen-independent manner in HIV-infected individuals. J Immunol 192, 1732-1744   DOI
33 Zarozinski CC and Welsh RM (1997) Minimal bystander activation of CD8 T cells during the virus-induced poly-clonal T cell response. J Exp Med 185, 1629-1639   DOI
34 Younes SA, Freeman ML, Mudd JC et al (2016) IL-15 promotes activation and expansion of CD8+ T cells in HIV-1 infection. J Clin Invest 126, 2745-2756   DOI
35 Seo IH, Eun HS, Kim JK et al (2021) IL-15 enhances CCR5-mediated migration of memory CD8(+) T cells by upregulating CCR5 expression in the absence of TCR stimulation. Cell Rep 36, 109438   DOI
36 Walsh JT, Hendrix S, Boato F et al (2015) MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4. J Clin Invest 125, 699-714   DOI
37 van Wilgenburg B, Scherwitzl I, Hutchinson EC et al (2016) MAIT cells are activated during human viral infections. Nat Commun 7, 11653   DOI
38 Danahy DB, Berton RR and Badovinac VP (2020) Cutting edge: antitumor immunity by pathogen-specific CD8 T cells in the absence of cognate antigen recognition. J Immunol 204, 1431-1435   DOI
39 Lee HG, Lee JU, Kim DH, Lim S, Kang I and Choi JM (2019) Pathogenic function of bystander-activated memory-like CD4(+) T cells in autoimmune encephalomyelitis. Nat Commun 10, 709   DOI
40 Simoni Y, Becht E, Fehlings M et al (2018) Bystander CD8(+) T cells are abundant and phenotypically distinct in human tumour infiltrates. Nature 557, 575-579   DOI
41 Tough DF, Sun S and Sprent J (1997) T cell stimulation in vivo by lipopolysaccharide (LPS). J Exp Med 185, 2089-2094   DOI
42 Murali-Krishna K, Altman JD, Suresh M et al (1998) Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. Immunity 8, 177-187   DOI
43 Eberl G, Brawand P and MacDonald HR (2000) Selective bystander proliferation of memory CD4+ and CD8+ T cells upon NK T or T cell activation. J Immunol 165, 4305-4311   DOI
44 Guo L, Huang Y, Chen X, Hu-Li J, Urban JF Jr and Paul WE (2015) Innate immunological function of TH2 cells in vivo. Nat Immunol 16, 1051-1059   DOI
45 Gangappa S, Deshpande SP and Rouse BT (1999) Bystander activation of CD4(+) T cells can represent an exclusive means of immunopathology in a virus infection. Eur J Immunol 29, 3674-3682   DOI
46 Yang HY, Dundon PL, Nahill SR and Welsh RM (1989) Virus-induced polyclonal cytotoxic T lymphocyte stimulation. J Immunol 142, 1710-1718
47 Unutmaz D, Pileri P and Abrignani S (1994) Antigen-independent activation of naive and memory resting T cells by a cytokine combination. J Exp Med 180, 1159-1164   DOI
48 Polley R, Zubairi S and Kaye PM (2005) The fate of heterologous CD4+ T cells during Leishmania donovani infection. Eur J Immunol 35, 498-504   DOI
49 Guo L, Wei G, Zhu J et al (2009) IL-1 family members and STAT activators induce cytokine production by Th2, Th17, and Th1 cells. Proc Natl Acad Sci U S A 106, 13463-13468   DOI
50 Pellicci DG, Koay HF and Berzins SP (2020) Thymic development of unconventional T cells: how NKT cells, MAIT cells and γδ T cells emerge. Nat Rev Immunol 20, 756-770   DOI
51 Leite-De-Moraes MC, Hameg A, Arnould A et al (1999) A distinct IL-18-induced pathway to fully activate NK T lymphocytes independently from TCR engagement. J Immunol 163, 5871-5876
52 Ma R, Yuan D, Guo Y, Yan R and Li K (2020) Immune effects of γδ T cells in colorectal cancer: a review. Front Immunol 11, 1600   DOI
53 Horwitz MS, Bradley LM, Harbertson J, Krahl T, Lee J and Sarvetnick N (1998) Diabetes induced by Coxsackie virus: initiation by bystander damage and not molecular mimicry. Nat Med 4, 781-785   DOI
54 Lertmemongkolchai G, Cai G, Hunter CA and Bancroft GJ (2001) Bystander activation of CD8+ T cells contributes to the rapid production of IFN-gamma in response to bacterial pathogens. J Immunol 166, 1097-1105   DOI
55 Duhen T, Duhen R, Montler R et al (2018) Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors. Nat Commun 9, 2724   DOI
56 Brennan FM, Smith NM, Owen S et al (2008) Resting CD4+ effector memory T cells are precursors of bystander-activated effectors: a surrogate model of rheumatoid arthritis synovial T-cell function. Arthritis Res Ther 10, R36   DOI
57 Rouxel O, Da Silva J, Beaudoin L et al (2017) Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes. Nat Immunol 18, 1321-1331   DOI
58 Markle JG, Mortin-Toth S, Wong AS, Geng L, Hayday A and Danska JS (2013) γδ T cells are essential effectors of type 1 diabetes in the nonobese diabetic mouse model. J Immunol 190, 5392-5401   DOI
59 Ferreira TB, Hygino J, Wing AC et al (2018) Different interleukin-17-secreting Toll-like receptor(+) T-cell subsets are associated with disease activity in multiple sclerosis. Immunology 154, 239-252   DOI
60 Jones RE, Kay T, Keller T and Bourdette D (2003) Nonmyelinspecific T cells accelerate development of central nervous system APC and increase susceptibility to experimental autoimmune encephalomyelitis. J Immunol 170, 831-837   DOI
61 Gregorova M, Morse D, Brignoli T et al (2020) Post-acute COVID-19 associated with evidence of bystander T-cell activation and a recurring antibiotic-resistant bacterial pneumonia. Elife 9, e63430   DOI
62 Scheper W, Kelderman S, Fanchi LF et al (2019) Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers. Nat Med 25, 89-94   DOI
63 Rosato PC, Wijeyesinghe S, Stolley JM et al (2019) Virusspecific memory T cells populate tumors and can be repurposed for tumor immunotherapy. Nat Commun 10, 567   DOI
64 Reynolds JM, Pappu BP, Peng J et al (2010) Toll-like receptor 2 signaling in CD4(+) T lymphocytes promotes T helper 17 responses and regulates the pathogenesis of autoimmune disease. Immunity 32, 692-702   DOI
65 Chu T, Tyznik AJ, Roepke S et al (2013) Bystander-activated memory CD8 T cells control early pathogen load in an innate-like, NKG2D-dependent manner. Cell Rep 3, 701-708   DOI
66 Lees JR, Sim J and Russell JH (2010) Encephalitogenic T-cells increase numbers of CNS T-cells regardless of antigen specificity by both increasing T-cell entry and preventing egress. J Neuroimmunol 220, 10-16   DOI