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

Background/Aims: Human invariant natural killer T (iNKT) cells express a TCR V alpha 24-J alpha Q paired with V beta 11 and are activated by a surrogate ligand, a-galactosylceramide (alpha GalCer). The iNKT cells are involved in the regulation of antiviral 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 aGalCer 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 alpha GalCer-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-gamma-producing iNKT cells reactive to aGalCer 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 aGalCer, expanded iNKT cells from the patients secreted IFN-gamma 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. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.