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Altered expression of T cell Immunoglobulin-Mucin (TIM) molecules in bronchoalveolar lavage CD4+ T cells in sarcoidosis

DOI: 10.1186/1465-9921-10-42

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Abstract:

We used real-time polymerase chain reaction to investigate the differential gene expression of TIM-1 and TIM-3 as well as a few Th1 and Th2 cytokines (IL-2, IFN-γ, IL-4, IL-5 and IL-13) in CD4+ T cells isolated from bronchoalveolar lavage fluid (BALF) of patients (n = 28) and healthy controls (n = 8). Using flow cytometry, we were also able to analyse TIM-3 protein expression in 10 patients and 6 healthy controls.A decreased TIM-3 mRNA (p < 0.05) and protein (p < 0.05) expression was observed in patients, and the level of TIM-3 mRNA correlated negatively with the CD4/CD8 T cell ratio in BALF cells of patients. Compared to a distinct subgroup of patients i.e. those with L?fgren's syndrome, BALF CD4+ T cells from non- L?fgren's patients expressed decreased mRNA levels of TIM-1 (p < 0.05). mRNA expression of IL-2 was increased in patients (p < 0.01) and non-L?fgren's patients expressed significantly higher levels of IFN-γ mRNA (p < 0.05) versus patients with L?fgren's syndrome.These findings are the first data on the expression of TIM-1 and TIM-3 molecules in sarcoidosis. The reduced TIM-3 expression in the lungs of patients may result in a defective T cell ability to control the Th1 immune response and could thus contribute to the pathogenesis of sarcoidosis. The down-regulated TIM-1 expression in non-L?fgren'spatients is in agreement with an exaggerated Th1 response in these patients.Sarcoidosis is a T helper (Th) 1-mediated inflammatory disease with unknown aetiology, characterized by the formation of noncaseating granulomas, and involving accumulations of macrophages and T cells, primarily affecting the lungs [1]. In pulmonary sarcoidosis, an acute onset usually indicates a self-limiting disease course, whereas an insidious onset may be followed by persistent disease with a risk for fibrosis [1]. An imbalance in the expression of Th1/Th2 cytokines by alveolar cells has been suggested to be of importance for the outcome of a pulmonary immune response in sarcoidosis

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