Aberrant Fas ligand expression in lymphocytes in patients with Behçet's disease.
BACKGROUND
Defects in immune responses have been reported in patients with Behçet's disease (BD). To further characterize the immune dysfunction and its contribution to the pathogenesis, we have studied Fas ligand (FasL) expression in peripheral blood lymphocytes (PBL) and mononuclear cells in the skin lesions in patients with BD.


METHODS
FasL expression in PBL was studied with RT-PCR and immunoblotting with rabbit anti-human FasL antibody. We studied the expression of FasL in cryostat sections of biopsy specimens of erythema nodosum lesions from 4 patients with BD and of a genital ulcer lesion in another patient using immunohistochemical staining. Apoptotic cell death was detected with the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method.


RESULTS
We found that FasL mRNA and FasL protein expression was detected marginally in the unstimulated PBL, and was induced upon activation in normal individuals. PBL from patients with BD exhibited an enhanced expression of FasL mRNA and FasL protein without in vitro stimulation. Moreover, mitogen stimulation failed to augment FasL expression of their lymphocytes, suggesting a dysregulation of FasL expression of PBL in patients with BD. The skin biopsy specimens revealed that cells infiltrating into skin lesions expressed FasL and there were several TUNEL staining-positive cells in the lesions, suggesting that Fas/FasL-mediated apoptosis is involved in the development of the skin lesion and thus may be associated with the pathogenesis.


CONCLUSIONS
We found an excessive expression of FasL in circulating as well as skin-infiltrating lymphocytes and the presence of apoptotic cells in the skin lesions, suggesting that lymphocytes expressing FasL aberrantly may play a role in the development and pathogenesis of BD.
Wakisaka
Sueshige
S
Department of Immunology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
Takeba
Yuko
Y
Mihara
Shoji
S
Takeno
Mhoso
M
Yamamoto
Shoso
S
Sakane
Tsuyoshi
T
Suzuki
Noboru
N
D000328:Adult; D017209:Apoptosis / Q000276:immunology; D001528:Behcet Syndrome / Q000097:blood / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D053222:Fas Ligand Protein; D006801:Humans; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger