Regulatory and Th17 Cells in Antiviral Immune Responses

Regulatory T cells (Tregs) play a central role in regulating immune responses by generally suppressing or downregulating the induction and proliferation of effector T cells. Although Tregs are important for the maintenance of tolerance to self-antigens, they can also suppress the immune response to pathogens. Th17 cells (so called because they secrete interleukin 17, IL-17) are related to Tregs, but play an important role in maintaining mucosal barriers and contributing to pathogen clearance at mucosal surfaces. Interestingly, the signals that elicit Th17 to differentiation also inhibit Treg differentiation, indicating a strong regulatory relationship between the two cell types. With this in mind, Liu and colleagues note that the regulation of the balance between Tregs and Th17 cells was poorly understood in hepatitis C virus (HCV) infection. Based on a recent report that toll-like receptor (TLR) 2 regulated the balance of Tregs/Th17 functions in multiple sclerosis, the authors investigated the role of TLR2 in HCV infection. Analysis of chronic hepatitis C patients receiving interferon therapy and normal controls revealed that Tregs, but not Th17 cells, from chronic hepatitis C patients expressed higher levels of TLR2 than from controls. Moreover, stimulation with TLR2 agonists modulated the Treg/Th17 cell balance in patients with chronic hepatitis C by inducing Tregs to produce IL-10 and enhancing cell-to-cell contact inhibition of effector T cells. The data suggest that it might be possible to manipulate the Treg/Th17 differentiation pathway to treat chronic HCV infection.

In a second article that addressed the ratio of Treg to Th17 cells during chronic viral infection, Wang and colleagues have analyzed patients who are chronically infected with hepatitis B virus (HBV). Specifically, the authors investigated the dynamic balance of Treg/Th17 cells in patients treated with telbivudine. The data indicate that telbivudine increased the frequency of Th17 cells and associated cytokines and downregulated the frequency of Treg cells and level of transforming growth factor (TGF)-β, corresponding to a decrease of Treg/Th17 ratio. The Treg/Th17 ratio during treatment also strongly predicted seroconversion against the HBV envelope protein, which might be useful in the clinical setting.

Three other articles in this issue of Viral Immunology addressed issues related to vaccination. Cuffia et al. have analyzed the strains used for immunization against rotavirus collected from children in Argentina. The authors have identified substitutions in the G protein of circulating strains that may result in escape from antibody neutralization. These findings may be important for the long-term application of the vaccine. Pugh et al. have focused on the live vaccinia virus (VACV) smallpox vaccine and the fact that viral shedding from the vaccination site can result in autoinoculation and contact transmission. The authors had previously found that the application of povidone iodine ointment (PIO) to the scarification site reduced viral shedding without altering the antibody response. In the current article, they show that the postvaccination antibody response to 11 individual VACV antigens was significantly greater than the prevaccination response. These findings further support the topical application of PIO, starting on day 7, to reduce the viral shedding associated with smallpox vaccination. Joshi and Arankalle point out that hepatitis E virus is a predominant cause of sporadic acute hepatitis in adults and waterborne epidemics, leading to high mortality rate in pregnant women. Vaccine development is an urgent priority. In this context, the authors evaluated a liposome-adjuvanted recombinant neutralizing epitope protein (rNEp) from a structural capsid protein in mice and rhesus macaques. The data indicate that a balanced Th1/Th2 response was elicited with a liposome-adjuvanted rNEp, whereas a Th2 bias was elicited with an alum-adjuvanted rNEp. The data suggest that the liposome-adjuvanted rNEp is a better immunogen for this vaccine.

Finally, two articles address other aspects of the immune response to infection. Huang et al. present data on different reference genes to be used for expression analysis on anti-infection genes in porcine intestinal epithelial cells after porcine sapelovirus infection. Their results identify two genes with stable expression that are recommended as appropriate reference genes for these types of studies. Cansanção and colleagues highlight the importance of an IL1β polymorphism in the development of clinical symptoms of dengue virus infection.

I would like to thank all of the authors for their excellent contributions to the Journal and all of the reviewers for their efforts to maintain high quality of the published articles.