title: Impaired IFN-gamma production of Valpha24 NKT cells in non-remitting sarcoidosis.
abstract: Sarcoidosis is a systemic disorder associated with granuloma characterized by an abnormal T(h)1-type cytokine production and accumulation of T(h)1 CD4 T cells in the granuloma lesions, suggesting an importance of T(h)1 responses in sarcoidosis. However, the pathogenesis of sarcoidosis remains to be solved. Here, we investigated the nature of V(alpha)24 NKT cells with immunoregulatory functions in sarcoidosis. Patients with non-remitting sarcoidosis displayed a decrease in the number of V(alpha)24 NKT cells in peripheral blood, but an accumulation of these cells in granulomatous lesions. When stimulated with the specific glycolipid ligand, alpha-galactosylceramide, peripheral blood V(alpha)24 NKT cells from patients with non-remitting disease produced significantly less IFN-gamma than those from healthy volunteers, but normal levels of IL-4. The reduced IFN-gamma production was observed only in V(alpha)24 NKT cells and not conventional CD4 T cells, but was normal in patients with remitting disease, suggesting that non-remitting sarcoidosis involves an insufficient IFN-gamma production of V(alpha)24 NKT cells which is well correlated with disease activity. Thus, these results suggest that V(alpha)24 NKT cells play a crucial role in the disease status of sarcoidosis.
authors.affiliation: Department of Molecular Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Seino
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Yamada
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Motohashi
authors.forename: Junzo
authors.initials: J
authors.lastname: Koike
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sugaya
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kuriyama
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Asano
authors.forename: Tomiyasu
authors.initials: T
authors.lastname: Tsuda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wakao
authors.forename: Michishige
authors.initials: M
authors.lastname: Harada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kojo
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
mesh_terms: D000328:Adult; D001327:Autoimmune Diseases / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006099:Granuloma / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017565:Sarcoidosis, Pulmonary / Q000276:immunology*
chemical_list: D015847:Interleukin-4; D007371:Interferon-gamma