Enhanced ability of peripheral invariant natural killer T cells to produce IL-13 in chronic hepatitis C virus infection

Background/Aims Human invariant natural killer T (iNKT) cells express a TCR Vα24-JαQ paired with Vβ11 and are activated by a surrogate ligand, α-galactosylceramide (αGalCer). The iNKT cells are involved in the regulation of anti-viral immune responses; however, little is known about their roles in hepatitis C virus (HCV) infection. Methods We compared the frequency of peripheral iNKT cells and their cytokine producing capacity reactive to αGalCer between chronically HCV-infected patients and healthy subjects. Cytokine production of freshly isolated iNKT cells were analyzed by ELISPOT. Activated iNKT cells were obtained by culture with αGalCer-loaded dendritic cells (DCs) and re-stimulated with them for the measurement of cytokine production. Results The frequencies of iNKT cells were not different between HCV-infected patients and healthy subjects. The number of fresh IFN-γ-producing iNKT cells reactive to αGalCer was not different between the patients and controls, whereas fresh iNKT cells produced negligible amounts of Th2 cytokines regardless of HCV infection. In response to αGalCer, expanded iNKT cells from the patients secreted IFN-γ comparable in amount to controls, whereas they released significantly more IL-13 than cells from controls. Conclusions Activated iNKT cells from HCV-infected patients gain more ability to secrete IL-13 than those from healthy subjects.