Changes of Treg and Th17 cells balance in the development of acute and chronic hepatitis B virus infection

Department of Infectious Diseases, Changhai Hospital, Second Military Medical University, Shanghai, China.
BMC Gastroenterology (Impact Factor: 2.37). 05/2012; 12(1):43. DOI: 10.1186/1471-230X-12-43
Source: PubMed


Many studies suggest that in chronic hepatitis B virus (HBV) infection regulate T (Treg) cells and interlukin-17-producing T help cells (Th17) are mutually antagonistic in the immune response. This study is aimed to reveal the cell differentiation environment and the significance of Treg and Th17 balance in the development of acute and chronic HBV infection.
Ten patients with acute HBV infection (AHB) and forty-eight patients with chronic HBV infection, including 12 asymptomatic HBV carriers (HBV carriers), 18 chronic hepatitis B patients (CHB) and 18 acute-on-chronic HBV-related liver failure (ACHBLF) were enrolled. Treg and Th17 cells differentiation related cytokine levels were detected by using ELISA. Flow cytometry was employed to count the Treg and Th17 frequency in peripheral blood.
Compared to health controls both AHB and ACHBLF patients favoured Th17 cell differentiation, accompanied by a higher proportion of peripheral Th17 cells (P < 0.01) and high level of interleukin-17A (IL-17A) (P < 0.01). However, asymptomatic HBV carriers and CHB were conducive to Treg cell differentiation. In AHB and ACHBLF, peripheral blood IL-17A + CD4 + T cell frequency increased significantly compared with healthy controls. Changes of Treg and Th17 cell frequency were not completely consistent. Both CHB and ACHBLF had lower level of Treg/Th17 ratio than in health control (P < 0.05). Both plasm IL-17A levels (r = -0.72, p<0.001) and Th17 frequency(r = -0.49, p = 0.0003) negatively correlated with plasma HBV DNA load in patients with chronic HBV infection. In addition, both Th17 frequency and plasm IL-17A levels positively correlated with ALT (r = 0.33,p = 0.01 Vs r = 0.29, p = 0.04) and total bilirubin levels (r = 0.72,p<0.0001 Vs r = 0.53, p = 0.0001) in these chronic HBV-infected subjects. However, for AHB there were positive correlation between both Th17 frequency (r = 0.64, p = 0.04) and plasm IL-17A levels (r = 0.69, p = 0.02) with serum ALT levels, but no significant correlation between both HBV DNA level and total bilirubin level with Th17 frequency or plasm IL-17A levels were found. Furthermore, Treg/Th17 ratio was negatively correlated with total bilirubin levels (r = -0.41, p = 0.004) in chronic HBV-infected patients, especially in patients with ACHBLF (r = -0.69, p = 0.001) and positively correlated with viral load in these chronic HBV-infected subjects (r = 0.55, p<0.0001).
Th17 cells are involved in acute and chronic HBV infection, especially in AHB and ACHBLF. CHB and ACHBLF patients manifested obvious Treg/Th17 ratio imbalance, which might be linked to disease progression and the continuous HBV infection.

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    • "The frequencies of Treg and Th17 cells are reported to increase in the peripheral blood of HBV patients [139, 140]. Th17 levels [141, 142] and the Treg/TH17 ratio appear to have a crucial role in the occurrence, development, and outcome of HBV [142, 143] and could be used as indicators of inflammation that may predict progression to fibrosis [144]. Hence, Th17 cells can contribute to immune activation and disease aggravation in patients with chronic HBV infection [138, 145], because of the correlation of Th17 cells with serum alanine aminotransferase levels [139]. "
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    ABSTRACT: The view of CD4 T-cell-mediated immunity as a balance between distinct lineages of Th1 and Th2 cells has changed dramatically. Identification of the IL-17 family of cytokines and of the fact that IL-23 mediates the expansion of IL-17-producing T cells uncovered a new subset of Th cells designated Th17 cells, which have emerged as a third independent T-cell subset that may play an essential role in protection against certain extracellular pathogens. Moreover, Th17 cells have been extensively analyzed because of their strong association with inflammatory disorders and autoimmune diseases. Also, they appear to be critical for controlling these disorders. Similar to Th1 and Th2 cells, Th17 cells require specific cytokines and transcription factors for their differentiation. Th17 cells have been characterized as one of the major pathogenic Th cell populations underlying the development of many autoimmune diseases, and they are enhanced and stabilized by IL-23. The characteristics of Th17 cells, cytokines, and their sources, as well as their role in infectious and autoimmune diseases, are discussed in this review.
    08/2014; 2014(9):651503. DOI:10.1155/2014/651503
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    • "Despite a number of reports indicating that the frequencies of Tregs are closely associated with disease progression in HBV-infected patients [4,15,16,35], the function of Tregs in HBV-associated pathogenesis is just beginning to be explored. Tregs and the production of the suppressive cytokine IL-10 are crucial to tolerance induction in a mouse model of Con A hepatitis [19]. "
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    PLoS ONE 07/2013; 8(7):e68997. DOI:10.1371/journal.pone.0068997 · 3.23 Impact Factor
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    • "These are IL-17-producing Th17 cells that contribute to the progression of inflammation [10] [11] and Foxp3 + T regulatory cells which are natural suppressors that control overactive cells [12] [13]. A balance between Th17 and Treg subsets is crucial for immune homeostasis, however it was shown to be impaired in various clinical disorders [14] [15] [16] [17] [18] [19] [20]. The balance between Tregs and Th17 is controlled by IL-6. "
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    Mediators of Inflammation 02/2013; 2013(2):205284. DOI:10.1155/2013/205284 · 3.24 Impact Factor
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