Changes in natural killer T cells subsets during therapy in type C hepatitis and hepatocellular carcinoma

Natural killer T (NKT) cells share features of both classical T cells and NK cells. NKT are heterogenous populations, and recognize glycolipids associated with CD1d molecule. We investigated Th1/Th2 cytokine production as well as frequency and phenotype of circulating NKT cells in 14 healthy subjects and in patients during therapy with type C chronic hepatitis (CH; 14 cases) and hepatocellular carcinoma (HCC; 13 cases). Peripheral blood mononuclear cells (PBMC) were obtained before and 2 weeks later interferon (IFN)/ribavirin and radiofrequency ablation therapy for CH and HCC, respectively. PBMC were cultured for 10 days with α-galactosylceramide (α-GalCer) and interleukin-2 (IL-2). Frequencies and IFN-γ/IL-4 production of NKT cells were analyzed using flow cytometry. Intrahepatic lymphocytes were analyzed in seven CH patients with liver biopsy specimen. Prevalence of circulating Vα24+CD3+ T cells was 0.9 ± 0.9% of PBMC for controls and increased to 8.5 ± 8.9% (p < 0.001) in response to α-GalCel. Similar frequency and expansion were noted in CH. The frequency increased during therapy. The prevalence in HCC tended to be high compared to controls and response to α-GalCel was well. Although frequency of Vα24+Vβ11+CD3+ T cells was low in all groups, the distribution pattern was similar to Vα24+Vβ11−CD3+ T cells. Prevalence of CD56+CD3+ T cells was low independent of therapy in CH (2-3%) compared to 5.0 ± 4.0% of controls, although response to α-GalCel was not impaired. IFN-γ production of Vα24+CD3+ T cells did not differ among groups, but became greater after treatment in contrast to lowered IL-4 production. Frequencies of NKT populations were higher in liver than in peripheral blood. Our study suggests that CD1d-reactive T cells have distinct distribution in different populations and therapy for patients alters cytokine response of NKT cells.