Impaired IFN-γ production of V_α24 NKT cells in non-remitting sarcoidosis

Sarcoidosis is a systemic disorder associated with granuloma characterized by an abnormal T_h1-type cytokine production and accumulation of T_h1 CD4 T cells in the granuloma lesions, suggesting an importance of T_h1 responses in sarcoidosis. However, the pathogenesis of sarcoidosis remains to be solved. Here, we investigated the nature of V_α24 NKT cells with immunoregulatory functions in sarcoidosis. Patients with non-remitting sarcoidosis displayed a decrease in the number of V_α24 NKT cells in peripheral blood, but an accumulation of these cells in granulomatous lesions. When stimulated with the specific glycolipid ligand, α-galactosylceramide, peripheral blood V_α24 NKT cells from patients with non-remitting disease produced significantly less IFN-γ than those from healthy volunteers, but normal levels of IL-4. The reduced IFN-γ production was observed only in V_α24 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-γ production of V_α24 NKT cells which is well correlated with disease activity. Thus, these results suggest that V_α24 NKT cells play a crucial role in the disease status of sarcoidosis.