Administration of interleukin-2 induces major histocompatibility complex class II expression on the biliary epithelial cells, possibly through endogenous interferon-gamma production.
In various organ-specific autoimmune diseases, aberrant expression of major histocompatibility complex class II antigens on each target epithelial cell has been reported. Some researchers have attempted to link this phenomenon to the antigen-presenting capacity and the induction of autoimmunity, whereas others think it might serve as a peripheral mechanism for the induction and the maintenance of self-tolerance in autoreactive T cells. In this study, we showed that intraperitoneal administration of interleukin-2 (1.2 x 10(6) IU/kg) to 4-wk-old male BALB/c mice for 35 consecutive days induced lymphocyte infiltration around bile ducts in the liver and major histocompatibility complex class II expression on biliary epithelial cells, which was immunoelectron microscopically confined to the luminal cell surface. Immunohistochemically, lymphocytes accumulating around bile ducts were mainly T cells, positive for CD3, L3T4 and H-2 class II molecules, and a few of them were positive for Lyt-2 and negative for immunoglobulin. Half of the infiltrates were positive for asialo GM1, and one-third was positive for interferon-gamma. Interferon-gamma-positive, L3T4-positive cells were detected in mirror sections. However, neither the destruction of biliary epithelial cells nor the presence of granulomas was observed. Autoantibodies were serologically undetectable. The existence of interferon-gamma-positive cells in the lesion and the fact that intravenous administration of anti-interferon-gamma twice a week completely inhibited the lymphocyte infiltration and the major histocompatibility complex class II expression on biliary epithelial cells suggested that these changes were induced through endogenous interferon-gamma production.(ABSTRACT TRUNCATED AT 250 WORDS)
Himeno
H
H
1st Department of Medicine, Kochi Medical School, Japan.
Saibara
T
T
Onishi
S
S
Yamamoto
Y
Y
Enzan
H
H
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology; D001652:Bile Ducts / Q000187:drug effects* / Q000276:immunology; D015704:CD4 Antigens / Q000032:analysis; D004848:Epithelium / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D007371:Interferon-gamma