Abstract
Invariant NKT (iNKT) cells are involved in the pathogenesis of various infectious diseases. However, their role in hepatitis B virus (HBV) infection is not fully understood, especially in human species. In this study, 35 chronic hepatitis B (CHB) patients, 25 inactive carriers (IC) and 36 healthy controls (HC) were enrolled and the proportions of circulating iNKT cells in fresh isolated peripheral blood mononuclear cells (PBMC) were detected by flow cytometry. A longitudinal analysis was also conducted in 19 CHB patients who received antiviral therapy with telbivudine. Thereafter, the immune functions of iNKT cells were evaluated by cytokine secretion and a two-chamber technique. The median frequency of circulating iNKT cells in CHB patients (0.13%) was lower than that in HC (0.24%, P = 0.01) and IC (0.19%, P = 0.02), and increased significantly during antiviral therapy with telbivudine (P = 0.0176). The expressions of CC chemokine receptor 5 (CCR5) and CCR6 were dramatically higher on iNKT cells (82.83%±9.87%, 67.67%±16.83% respectively) than on conventional T cells (30.5%±5.65%, 14.02%±5.92%, both P<0.001) in CHB patients. Furthermore, iNKT cells could migrate toward the CC chemokine ligand 5. Patients with a high ratio (≥1.0) of CD4−/CD4+ iNKT cells at baseline had a higher rate (58.33%) of HBeAg seroconversion than those with a low ratio (<1.0, 0%, P = 0.0174). In conclusion, there is a low frequency of peripheral iNKT cells in CHB patients, which increases to normal levels with viral control. The ratio of CD4−/CD4+ iNKT cells at baseline may be a useful predictor for HBeAg seroconversion in CHB patients on telbivudine therapy.
Highlights
Worldwide, more than 300 million people suffer from chronic hepatitis B virus (HBV) infection, leading to a wide spectrum of liver diseases including chronic hepatitis B (CHB), cirrhosis, and hepatocellular carcinoma [1]
Circulating Invariant NKT (iNKT) cells are decreased in CHB patients We first compared the frequencies of peripheral iNKT cells in subjects from the healthy controls (HC), CHB and inactive carriers (IC) groups. iNKT cells were detected by flow cytometry using a monoclonal antibody 6B11 (Fig. 1A), which reacts with the complementarity determining region 3 (CDR3) of the Va24-Ja18 T cell receptor of human iNKT cells [25]
We found that the frequency of iNKT cells in CHB patients (0.13%, 0.027%–1.071%) was significantly lower than that in HC (0.24%, 0.064%–0.81%, P = 0.0143) and IC (0.19%, 0.06%– 0.38%, P = 0.0235)
Summary
More than 300 million people suffer from chronic hepatitis B virus (HBV) infection, leading to a wide spectrum of liver diseases including chronic hepatitis B (CHB), cirrhosis, and hepatocellular carcinoma [1]. Invariant NKT (iNKT) cells are a unique group of T lymphocytes that express an identical T cell antigen receptor (TCR) a chain, Va14-Ja18 in mice and Va24-Ja18 in humans [3]. INKT cells differ from conventional T lymphocytes in that they recognize lipid or glycolipid antigens presented by the MHC class I-like molecule CD1d. INKT cells comprise a very small proportion of peripheral T cells, about 1% in mice and 0.2% in humans, they seem to play important roles in regulating a number of immune responses, including transplant rejection, cancer, autoimmunity, allergy, and infection [5,6]
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