Abstract
The cluster of differentiation protein complex, CD80/CD86, regulates Th1/Th2 differentiation in autoimmune disease. In order to establish the effects of CD80/CD86 on Th17 cell differentiation in acute viral myocarditis (VMC), we infected C57BL/6 mice with Coxsackie virus B3 (CVB3) and examined the effects of the treatment with anti-CD80/CD86 monoclonal antibodies (mAbs) on Th17 cell differentiation in vivo. The effects of anti-CD80/CD86 mAbs on Th17 cell differentiation were further evaluated in vitro. The treatment with anti-CD80 mAb induced marked suppression of Th17 cell differentiation and ROR-γt mRNA expression, whereas anti-CD86 mAb alone had no effect, both in vivo and in vitro. Our finding that CD80 regulates Th17 differentiation supports the potential utility of anti-CD80 mAb as an effective new immunotherapeutic target in acute VMC.
Similar content being viewed by others
References
Muthu, V., et al. 2014. Cardiac troponins: bench to bedside interpretation in cardiac disease. The American Journal of the Medical Sciences 347 (4): 331–337.
Deonarain, R., et al. 2004. Protective role for interferon-beta in coxsackievirus B3 infection. Circulation 110 (23): 3540–3543.
McManus, B.M., et al. 1993. Direct myocardial injury by enterovirus: a central role in the evolution of murine myocarditis. Clinical Immunology and Immunopathology 68 (2): 159–169.
Yue, Y., et al. 2011. Gene therapy with CCL2 (MCP-1) mutant protects CVB3-induced myocarditis by compromising Th1 polarization. Molecular Immunology 48 (4): 706–713.
Abston, E.D., et al. 2012. Th2 regulation of viral myocarditis in mice: different roles for TLR3 versus TRIF in progression to chronic disease. Clinical & Developmental Immunology 2012: 129486.
Fan, Y., et al. 2011. Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of coxsackievirus b3-induced viral myocarditis reduces myocardium inflammation. Virology Journal 8: 17.
Kuchroo, V.K., et al. 1995. B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: application to autoimmune disease therapy. Cell 80 (5): 707–718.
Lenschow, D.J., et al. 1996. CD28/B7 regulation of Th1 and Th2 subsets in the development of autoimmune diabetes. Immunity 5 (3): 285–293.
Park, J.J., et al. 2010. B7-H1/CD80 interaction is required for the induction and maintenance of peripheral T-cell tolerance. Blood 116 (8): 1291–1298.
Li, J.G., et al. 2016. CD80 and CD86 knockdown in dendritic cells regulates Th1/Th2 cytokine production in asthmatic mice. Experimental and Therapeutic Medicine 11 (3): 878–884.
Seko, Y., et al. 1998. Effects of in vivo administration of anti-B7-1/B7-2 monoclonal antibodies on murine acute myocarditis caused by coxsackievirus B3. Circulation Research 82 (5): 613–618.
Eriksson, U., et al. 2003. Dendritic cell-induced autoimmune heart failure requires cooperation between adaptive and innate immunity. Nature Medicine 9 (12): 1484–1490.
Ivanov, I.I., et al. 2006. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126 (6): 1121–1133.
O'Neill, S.K., et al. 2007. Expression of CD80/86 on B cells is essential for autoreactive T cell activation and the development of arthritis. Journal of Immunology 179 (8): 5109–5116.
Morbach, H., et al. 2011. Activated memory B cells may function as antigen-presenting cells in the joints of children with juvenile idiopathic arthritis. Arthritis and Rheumatism 63 (11): 3458–3466.
Menezes, S.M., et al. 2014. CD80+ and CD86+ B cells as biomarkers and possible therapeutic targets in HTLV-1 associated myelopathy/tropical spastic paraparesis and multiple sclerosis. Journal of Neuroinflammation 11: 18.
Racke, M.K., et al. 1995. Distinct roles for B7-1 (CD-80) and B7-2 (CD-86) in the initiation of experimental allergic encephalomyelitis. The Journal of Clinical Investigation 96 (5): 2195–2203.
Zeinstra, E., N. Wilczak, and J. De Keyser. 2003. Reactive astrocytes in chronic active lesions of multiple sclerosis express co-stimulatory molecules B7-1 and B7-2. Journal of Neuroimmunology 135 (1–2): 166–171.
Brown, J.A., et al. 2002. T helper differentiation in resistant and susceptible B7-deficient mice infected with Leishmania major. European Journal of Immunology 32 (6): 1764–1772.
Nolan, A., et al. 2009. Differential role for CD80 and CD86 in the regulation of the innate immune response in murine polymicrobial sepsis. PLoS One 4 (8): e6600.
Furukawa, Y., et al. 2000. Association of B7-1 co-stimulation with the development of graft arterial disease. The American Journal of Pathology 157 (2): 473–484.
Newton, S., et al. 2004. Sepsis-induced changes in macrophage co-stimulatory molecule expression: CD86 as a regulator of anti-inflammatory IL-10 response. Surgical Infections 5 (4): 375–383.
Nolan, A., et al. 2008. CD40 and CD80/86 act synergistically to regulate inflammation and mortality in polymicrobial sepsis. American Journal of Respiratory and Critical Care Medicine 177 (3): 301–308.
Genc, K., D.L. Dona, and A.T. Reder. 1997. Increased CD80(+) B cells in active multiple sclerosis and reversal by interferon beta-1b therapy. The Journal of Clinical Investigation 99 (11): 2664–2671.
Said, E.A., et al. 2016. Increased CD86 but not CD80 and PD-L1 expression on liver CD68+ cells during chronic HBV infection. PLoS One 11 (6): e0158265.
Park, H., et al. 2005. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nature Immunology 6 (11): 1133–1141.
Veldhoen, M., et al. 2006. TGF beta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24 (2): 179–189.
Mangan, P.R., et al. 2006. Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 441 (7090): 231–234.
Bettelli, E., et al. 2006. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441 (7090): 235–238.
Yang, F., et al. 2011. Expression of IL-23/Th17 pathway in a murine model of Coxsackie virus B3-induced viral myocarditis. Virology Journal 8: 301.
Qiu, S., et al., Cigarette smoke induction of interleukin-27/WSX-1 regulates the differentiation of Th1 and Th17 cells in a smoking mouse model of emphysema. Frontiers in Immunology, 2016. 7.
Long, Q., et al. 2016. Coxsackievirus B3 directly induced Th17 cell differentiation by inhibiting Nup98 expression in patients with acute viral myocarditis. Frontiers in Cellular and Infection Microbiology 6: 171.
YANG, F., et al. 2010. Alteration of Th17 cells in mice with coxsackie virus induced myocarditis. Zhonghua Xin Xue Guan Bing Za Zhi 38 (9): 790–793.
Funding
This work was supported by the National Natural Science Foundation of China (81670345).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Animal experiments were implemented in accordance with the protocols approved by the Guangxi Medical University Animal Ethics Committee.
Conflict of Interest
The authors declare that they have no conflicts of interest.
Additional information
Yanlan Huang and Yong Li are equal contributors.
Rights and permissions
About this article
Cite this article
Huang, Y., Li, Y., Wei, B. et al. CD80 Regulates Th17 Cell Differentiation in Coxsackie Virus B3-Induced Acute Myocarditis. Inflammation 41, 232–239 (2018). https://doi.org/10.1007/s10753-017-0681-7
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10753-017-0681-7