Altered expression of T cell immunoglobulin-mucin (TIM) molecules in bronchoalveolar lavage CD4+ T cells in sarcoidosis.
BACKGROUND
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.


METHODS
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-gamma, 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.


RESULTS
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 Löfgren's syndrome, BALF CD4+ T cells from non- Löfgren'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-Löfgren's patients expressed significantly higher levels of IFN-gamma mRNA (p < 0.05) versus patients with Löfgren's syndrome.


CONCLUSIONS
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'spatients is in agreement with an exaggerated Th1 response in these patients.
Idali
Farah
F
Department of Medicine, Unit of Respiratory Medicine, Karolinska Institutet, Stockholm, Sweden. farah.idali@ki.se
Wahlström
Jan
J
Dahlberg
Benita
B
Khademi
Mohsen
M
Olsson
Tomas
T
Eklund
Anders
A
Grunewald
Johan
J
D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005541:Forced Expiratory Volume; D015870:Gene Expression; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D000072596:Hepatitis A Virus Cellular Receptor 1; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D011991:Receptors, Virus / Q000235:genetics*; D012016:Reference Values; D012507:Sarcoidosis / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014797:Vital Capacity
C491143:HAVCR1 protein, human; C448908:HAVCR2 protein, human; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D000072596:Hepatitis A Virus Cellular Receptor 1; D000072597:Hepatitis A Virus Cellular Receptor 2; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D011991:Receptors, Virus