Coxsackievirus A16 infection stimulates imbalances of T cells in children

Luo,Qingming; Peng,Wanjun; Chen,Li

doi:10.3892/etm.2015.2405

Coxsackievirus A16 infection stimulates imbalances of T cells in children

Authors:
- Qingming Luo
- Wanjun Peng
- Li Chen
View Affiliations

Affiliations: Department of Pediatrics, Shilong People's Hospital, Dongguan, Guangdong 523320, P.R. China
Published online on: April 3, 2015 https://doi.org/10.3892/etm.2015.2405
Pages: 2213-2218

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Immune reaction plays a crucial role in the regulation of the progression of Coxsackievirus A16 (CA16)-infected hand, foot and mouth disease (HFMD). However, no details of T‑cell subset frequency or imbalance during the CA16 infection process have been revealed. In the present study, whether CA16‑induced HFMD changes the frequency of different T‑cell subsets and associated immune mediators was determined in children. The results indicate that the percentages of Th1 and Tc1 cells were significantly increased in children with HFMD compared with those in healthy children. In addition, the Th1/Th2 ratio and interferon (IFN)‑γ levels were significant higher in children with HFMD. Furthermore, the percentage of Th17 cells and the Th17/Treg ratio as well as interleukin (IL)‑17A levels were higher in HFMD cases. In conclusion, the present study demonstrated the dysregulation of T‑cell subsets following CA16 infection. The Th1/Th2 and Th17/Treg ratios were imbalanced following infection. Also, the imbalance Th1/Th2 and Th17/Treg ratios contributed to the increased levels of IFN‑γ and IL‑17A. Based on this information, the present study provides new insights for the future study of CA16-induced HFMD and offers new data of diagnostic and therapeutic value for CA16 infection.

View Figures

View References

1	Iwai M, Masaki A, Hasegawa S, et al: Genetic changes of coxsackievirus A16 and enterovirus 71 isolated from hand, foot, and mouth disease patients in Toyama, Japan between 1981 and 2007. Jpn J Infect Dis. 62:254–259. 2009.PubMed/NCBI
2	Zhang Y, Wang D, Yan D, et al: Molecular evidence of persistent epidemic and evolution of subgenotype B1 coxsackievirus A16-associated hand, foot, and mouth disease in China. J Clin Microbio. 48:619–622. 2010. View Article : Google Scholar
3	Ding NZ, Wang XM, Sun SW, Song Q, Li SN and He CQ: Appearance of mosaic enterovirus 71 in the 2008 outbreak of China. Virus Res. 145:157–161. 2009. View Article : Google Scholar : PubMed/NCBI
4	Liu LJ, Xu HM, Li XJ, et al: Co-detection in the pathogenesis of severe hand-foot-mouth disease. Arch Virol. 157:2219–2222. 2012. View Article : Google Scholar : PubMed/NCBI
5	Chang HW, Lin YW, Ho HM, et al: Protective efficacy of VP1-specific neutralizing antibody associated with a reduction of viral load and pro-inflammatory cytokines in human SCARB2-transgenic mice. PLoS One. 8:e698582013. View Article : Google Scholar : PubMed/NCBI
6	Wang SM, Lei HY, Huang MC, et al: Modulation of cytokine production by intravenous immunoglobulin in patients with enterovirus 71-associated brainstem encephalitis. J Clin Virol. 37:47–52. 2006. View Article : Google Scholar : PubMed/NCBI
7	Belkaid Y and Rouse BT: Natural regulatory T cells in infectious disease. Nat Immunol. 6:353–360. 2005. View Article : Google Scholar : PubMed/NCBI
8	Khong WX, Foo DG, Trasti SL, Tan EL and Alonso S: Sustained high levels of interleukin-6 contribute to the pathogenesis of enterovirus 71 in a neonate mouse model. J Virol. 85:3067–3076. 2011. View Article : Google Scholar : PubMed/NCBI
9	Li S, Cai C, Feng J, et al: Peripheral T lymphocyte subset imbalances in children with enterovirus 71-induced hand, foot and mouth disease. Virus Res. 180:84–91. 2014. View Article : Google Scholar : PubMed/NCBI
10	Gocinski BL and Tigelaar RE: Roles of CD4+ and CD8+ T cells in murine contact sensitivity revealed by in vivo monoclonal antibody depletion. J Immunol. 144:4121–4128. 1990.PubMed/NCBI
11	Lucey DR, Clerici M and Shearer GM: Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases. Clin Microbiol Rev. 9:532–562. 1996.PubMed/NCBI
12	Jutel M, Akdis M, Budak F, et al: IL-10 and TGF-β cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur J Immunol. 33:1205–1214. 2003. View Article : Google Scholar : PubMed/NCBI
13	Prabhakara R, Harro JM, Leid JG, Keegan AD, Prior ML and Shirtliff ME: Suppression of the inflammatory immune response prevents the development of chronic biofilm infection due to methicillin-resistant Staphylococcus aureus. Infect Immun. 79:5010–5018. 2011. View Article : Google Scholar : PubMed/NCBI
14	Xiao XL, Wu H, Li YJ, et al: Simultaneous detection of enterovirus 70 and coxsackievirus A24 variant by multiplex real-time RT-PCR using an internal control. J Virol Methods. 159:23–28. 2009. View Article : Google Scholar : PubMed/NCBI
15	Ooi MH, Wong SC, Podin Y, et al: Human enterovirus 71 disease in Sarawak, Malaysia: a prospective clinical, virological, and molecular epidemiological study. Clin Infect Dis. 44:646–656. 2007. View Article : Google Scholar : PubMed/NCBI
16	Mosmann TR, Cherwinski H, Bond MW, Giedlin MA and Coffman RL: Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 136:2348–2357. 1986.PubMed/NCBI
17	Myint AM, Leonard BE, Steinbusch HW and Kim YK: Th1, Th2, and Th3 cytokine alterations in major depression. J Affect Disord. 88:167–173. 2005. View Article : Google Scholar : PubMed/NCBI
18	Romagnani S, Maggi E and Del Prete G: An alternative view of the Th1/Th2 switch hypothesis in HIV infection. AIDS Res Hum Retroviruses. 10:iii–ix. 1994. View Article : Google Scholar : PubMed/NCBI
19	Kuo ML, Huang JL, Yeh KW, Li PS and Hsieh KH: Evaluation of Th1/Th2 ratio and cytokine production profile during acute exacerbation and convalescence in asthmatic children. Ann Allergy Asthma Immunol. 86:272–276. 2001. View Article : Google Scholar : PubMed/NCBI
20	Okazaki K, Uchida K, Ohana M, et al: Autoimmune-related pancreatitis is associated with autoantibodies and a Th1/Th2-type cellular immune response. Gastroenterology. 118:573–581. 2000. View Article : Google Scholar : PubMed/NCBI
21	Taams LS, Palmer DB, Akbar AN, Robinson DS, Brown Z and Hawrylowicz CM: Regulatory T cells in human disease and their potential for therapeutic manipulation. Immunology. 118:1–9. 2006. View Article : Google Scholar : PubMed/NCBI
22	Weaver CT and Hatton RD: Interplay between the TH17 and TReg cell lineages: a (co-) evolutionary perspective. Nat Rev Immunol. 9:883–889. 2009. View Article : Google Scholar : PubMed/NCBI
23	Zhu J and Paul WE: Heterogeneity and plasticity of T helper cells. Cell Res. 20:4–12. 2010. View Article : Google Scholar : PubMed/NCBI
24	Chen J, Tong J, Liu H, et al: Increased frequency of Th17 cells in the peripheral blood of children infected with enterovirus 71. J Med Virol. 84:763–767. 2012. View Article : Google Scholar : PubMed/NCBI
25	Ley K, Smith E and Stark MA: IL-17A-producing neutrophil-regulatory Tn lymphocytes. Immunol Res. 34:229–242. 2006. View Article : Google Scholar : PubMed/NCBI
26	Yang X, Wu Q, Wen B, Dai H, Zhuang Y and Yang J: Prevalent characteristics in children with hand-foot-mouth disease in the Kunming area in 2010. Zhongguo Dang Dai Er Ke Za Zhi. 14:192–194. 2012.[(In Chinese)]. PubMed/NCBI
27	Lin YW, Chang KC, Kao CM, Chang SP, Tung YY and Chen SH: Lymphocyte and antibody responses reduce enterovirus 71 lethality in mice by decreasing tissue viral loads. J Virol. 83:6477–6483. 2009. View Article : Google Scholar : PubMed/NCBI