title: Changes in natural killer T cells subsets during therapy in type C hepatitis and hepatocellular carcinoma.
abstract: 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 alpha-galactosylceramide (alpha-GalCer) and interleukin-2 (IL-2). Frequencies and IFN-gamma/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 Valpha24+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 alpha-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 alpha-GalCel was well. Although frequency of Valpha24+Vbeta11+CD3+ T cells was low in all groups, the distribution pattern was similar to Valpha24+Vbeta11-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 alpha-GalCel was not impaired. IFN-gamma production of Valpha24+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.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology and Research Center for Infectious Disease, Aichi Medical University School of Medicine, 21 Karimata Yazako, Nagakute-cho, Aichi-gun, Aichi-ken 480-1195, Aichi, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okumura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Tadashi
authors.initials: T
authors.lastname: Maeno
authors.forename: Ken
authors.initials: K
authors.lastname: Sato
authors.forename: Minoru
authors.initials: M
authors.lastname: Ayada
authors.forename: Naoki
authors.initials: N
authors.lastname: Hotta
authors.forename: Taeko
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fukuzawa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kakumu