Impaired IFN- production of V 24 NKT cells in non-remitting sarcoidosis

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Abstract
Sarcoidosis is a systemic disorder associated with granuloma characterized by an abnormal Th1‐type cytokine production and accumulation of Th1 CD4 T cells in the granuloma lesions, suggesting an importance of Th1 responses in sarcoidosis. However, the pathogenesis of sarcoidosis remains to be solved. Here, we investigated the nature of Vα24 NKT cells with immunoregulatory functions in sarcoidosis. Patients with non‐remitting sarcoidosis displayed a decrease in the number of Vα24 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 Vα24 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 Vα24 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 Vα24 NKT cells which is well correlated with disease activity. Thus, these results suggest that Vα24 NKT cells play a crucial role in the disease status of sarcoidosis.

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