Perforin down-regulation and adhesion molecules activation in pulmonary sarcoidosis: an induced sputum and BAL study.
BACKGROUND
Sarcoidosis is thought to be a T-helper type 1 cytokine-mediated disorder. Sputum induction has been proposed as a useful noninvasive method mainly for the assessment of airway diseases. However, it is unknown whether the balance of T-cytotoxic (Tc1) type 1 and Tc2 cells is altered in sarcoidosis.


OBJECTIVE
The primary aim of this study was to characterize the CD8+ T lymphocyte subpopulations in induced sputum from sarcoidosis patients, and to compare these subpopulations to those found in BAL fluid (BALF) from sarcoidosis patients. To further investigate the mechanism of the cytotoxic activity of CD8+ lymphocytes, we measured their perforin expression. Additionally, two adhesion molecules (CD62 and CD71), which are expressed on CD8+ T cells and may serve as novel immunologic markers, were detected.


METHODS
Department of Thoracic Medicine, University of Crete, and Department of Pneumonology, Democritus University of Thrace, Alexandroupolis, Greece.


METHODS
We prospectively studied 22 patients with sarcoidosis (median age, 48 years; age range, 25 to 65 years) and 10 healthy subjects (5 female and 5 male; median age, 39 years; age range, 26 to 60 years).


METHODS
The stimulation of lymphocytes with phorbol 12-myristate 13-acetate was followed by the use of double immunocytochemical methods to identify CD8+ interferon (IFN)-gamma producing cells (ie, Tc1) and CD8+ interleukin-4 producing cells (ie, Tc2).


RESULTS
We found a significant decrease in the prestimulation percentage of IFN-gamma-positive CD8+ T cells in the BALF (p = 0.001) and induced sputum (p = 0.001) of sarcoidosis patients compared to the number in samples from healthy control subjects. However, no significant difference was documented between lymphocyte subsets poststimulation. Decreased levels of perforin expression were found in BALF (p = 0.001) and induced sputum (p < 0.001) of sarcoidosis patients compared to those in control subjects. The adhesion molecules were significantly increased in both the BALF and induced sputum of the sarcoid population compared to those in healthy control subjects.


CONCLUSIONS
Our results suggest that inflammation could be effectively and noninvasively determined by using sputum induction in sarcoidosis patients. In addition, we have provided evidence suggesting the possibility that CD8+ lymphocytes might not play a major role in sarcoidosis.
Antoniou
Katerina M
KM
Head, Department of Pneumonology, Medical School University of Thrace, Alexandroupolis 68100, Greece.
Tsiligianni
Ioanna
I
Kyriakou
Despina
D
Tzanakis
Nikolaos
N
Tzouvelekis
Argyris
A
Siafakas
Nikolaos M
NM
Bouros
Demosthenes
D
D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D005260:Female; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D017565:Sarcoidosis, Pulmonary / Q000378:metabolism* / Q000473:pathology*; D013183:Sputum / Q000737:chemistry / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000502:physiology*
D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin