Impaired IFN-  production of V 24 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.

Neuro-ophthalmic sarcoidosis

“…This difference in sarcoidosis outcome has been associated with an imbalance in the expression of Th-1 and Th-2 cytokines [23,25]. A subset of immunoregulatory T cells has been implicated in the pathogenesis of sarcoidosis [22,[26][27][28]. Natural killer T (NKT) cells, which produce both Th-1 and Th-2 cytokines, are found at reduced levels in sarcoidosis patients [27,28].…”

“…A subset of immunoregulatory T cells has been implicated in the pathogenesis of sarcoidosis [22,[26][27][28]. Natural killer T (NKT) cells, which produce both Th-1 and Th-2 cytokines, are found at reduced levels in sarcoidosis patients [27,28]. Downregulation of NKT may be involved in the exaggerated T cell response in sarcoidosis.…”

A Phase I Study of α-Galactosylceramide (KRN7000)–Pulsed Dendritic Cells in Patients with Advanced and Recurrent Non–Small Cell Lung Cancer

“…The levels of IFN-g production in peripheral blood NKT cells were assessed by semiquantitative PCR. Two hundred thousand PBMCs separated from fresh peripheral blood were suspended in 200 AL of a complete culture medium in 96-well roundbottom plates and stimulated with 10 Ag/mL of immobilized anti-CD3q mAb (OKT3, American Type Culture Collection, Manassas, VA) for 14 hours as previously described (20,27). [12][13][14][15][16][17][18] (500 Ag/mL; Amersham Pharmacia Biotech, Piscataway, NJ), 2 AL deoxynucleotide triphosphates (2 mmol/L), 0.2 AL Superscript II (40 units, Life Technologies), and diethylpyrocarbonate double-distilled water in a total volume of 40 AL.…”

Individuals with Pulmonary Tuberculosis Have Lower Levels of Circulating CD1d‐Restricted NKT Cells

“…Circulating NKT levels are low in 2 diseases characterized by granulomas of the lungs: tuberculosis (figure 2A-2C) and sarcoidoisis [13]. NKT cells have been observed in granulomatous lesions of individuals with sarcoidosis [14] and leprosy [15], and Va14 + NKT cell-deficient mice have higher numbers of granulomas after infection with Mycobacterium bovis BCG [16]. Future longitudinal studies of both PBMCs and granulomatous lesions from individuals with pulmonary tuberculosis will help determine whether NKT cells home to the lungs from the circulation to contribute to granuloma formation.…”