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

• Main Authors: Olsson Tomas, Khademi Mohsen, Dahlberg Benita, Wahlström Jan, Idali Farah, Eklund Anders, Grunewald Johan
• Format: Article
• Language: English
• Published: BMC 2009-05-01
• Series: Respiratory Research
• Online Access: http://respiratory-research.com/content/10/1/42

<p>Abstract</p> <p>Background</p> <p>Activated T helper (Th)-1 pulmonary CD4⁺cells and their mediators are essential for the inflammation and granulomatous process in sarcoidosis. Recently, T-cell immunoglobulin and mucin domain (TIM) molecules were suggested to be important regulators of immune function. In this study, we wanted to investigate whether TIM molecules could play a role in sarcoidosis.</p> <p>Methods</p> <p>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 <it>(n = 28) </it>and healthy controls <it>(n = 8)</it>. Using flow cytometry, we were also able to analyse TIM-3 protein expression in 10 patients and 6 healthy controls.</p> <p>Results</p> <p>A decreased TIM-3 mRNA <it>(p < 0.05) </it>and protein <it>(p < 0.05) </it>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 Löfgren's syndrome, BALF CD4⁺T cells from non- Löfgren's patients expressed decreased mRNA levels of TIM-1 <it>(p < 0.05)</it>. mRNA expression of IL-2 was increased in patients <it>(p < 0.01) </it>and non-Löfgren's patients expressed significantly higher levels of IFN-γ mRNA <it>(p < 0.05</it>) versus patients with Löfgren's syndrome.</p> <p>Conclusion</p> <p>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-Löfgren's<b/>patients is in agreement with an exaggerated Th1 response in these patients.</p>