Mycobacterial heat shock protein-induced blood T lymphocytes subsets and cytokine pattern: comparison of sarcoidosis with tuberculosis and healthy controls.
OBJECTIVE
Sarcoidosis (SA) is a disorder of unknown aetiology. Mycobacterium tuberculosis heat shock proteins (Mtb-hsp) have been considered as causative agents of SA. The role of Mtb-hsp in the immune response in SA has not been investigated.


METHODS
Mtb-hsp-stimulated T-cell subsets and Th1/Th2 cytokine patterns in the supernatant from peripheral blood mononuclear cell cultures from 22 SA patients, 20 tuberculosis (TB) patients and 20 healthy volunteers were compared using flow cytometry.


RESULTS
In unstimulated cultures, a significantly higher percentage of CD8(+)alphabeta(+)T-cells were present in SA versus controls. Similarly there was a significantly increased IL-6 and decreased IL-4 level in SA and significantly lower INF-gamma, IL-2, IL-4, IL-10 production in TB versus controls. After Mtb-hsp stimulation, there was a significantly increased TNF-alpha, IL-6, IL-10 and decreased INF-gamma, IL-2, IL-4 production in SA and significantly increased TNF-alpha, IL-6 concentrations in TB versus controls. CD8(+)gammadelta(+)IL-4(+)T-cells were detected significantly less often in Mtb-hsp-induced cultures in SA versus controls. Comparing SA versus TB, CD4(+)gammadelta(+)TCR-cells were significantly increased in Mtb-hsp-induced cultures in TB versus controls and SA. Before stimulation, significantly increased IL-6, IL-10 and decreased IL-4 level in SA versus TB was revealed, whereas Mtb-hsp stimulation caused significantly increased IL-10 and decreased IL-4 concentrations in SA.


CONCLUSIONS
After Mtb-hsp stimulation, increased levels of pro-inflammatory cytokines, TNF-alpha and IL-6 were found in sera from SA and TB patients in comparison with healthy controls; SA patients demonstrated the lowest levels of IL-4 and the highest levels of IL-10.
Dubaniewicz
Anna
A
Department of Pathophysiology, Medical University of Gdańsk, Gdańsk, Poland. aduban@amg.gda.pl
Trzonkowski
Piotr
P
Dubaniewicz-Wybieralska
Mirosława
M
Dubaniewicz
Andrzej
A
Singh
Mahavir
M
Myśliwski
Andrzej
A
D000328:Adult; D001426:Bacterial Proteins / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D017565:Sarcoidosis, Pulmonary / Q000378:metabolism* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000378:metabolism* / Q000473:pathology; D014397:Tuberculosis, Pulmonary / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001426:Bacterial Proteins; D016207:Cytokines; D006360:Heat-Shock Proteins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4