Exocrinopathy resembling Sjögren's syndrome induced by a murine retrovirus.
BACKGROUND
Sjögren's syndrome (SS) is characterized by lymphocytic infiltration into, and destruction of exocrine glands, resulting in dryness of the mouth and eyes. The disease is considered to have an autoimmune etiology, however, its etiopathogenesis remains largely unknown. Recently, retrovirus is suggested to participate in the pathogenesis of SS, because SS-like lesions are reported in HIV infection or in human T cell leukemia virus type I infection. Moreover, human intracisternal A-type retroviral particles are reported to be detected in SS patients. During the course of our study on the histopathology of mice infected with a murine retrovirus, we happened to find SS-like exocrinopathy in those mice.


METHODS
Four-week-old C57BL/6 (B6) mice were injected intraperitoneally with LP-BM5 murine leukemia virus. This virus is known to induce splenomegaly, lymphadenopathy followed by lymphoid malignancy, and profound immunodeficiency in sensitive strains of mice. From 4 to 16 weeks after the virus inoculation, the infected mice were sacrificed and their submandibular and lacrimal glands were analyzed light and electron microscopically and immunohistochemically. The existence of the virus in the lesion in situ was also analyzed by the same method, and additionally by a polymerase chain reaction method.


RESULTS
Periductal lymphocytic infiltration into the submandibular and lacrimal glands was observed in all the virus-infected mice at 4 weeks after the infection and progressed with time. Extraglandular lymphocytic infiltration was also observed in liver, kidney, lung, and pancreas. Immunohistochemical examination revealed that most infiltrating cells into the glands were composed of CD3+ T cells (CD4-dominant), Mac-1+ cells, and B220+ cells. The virus genome was detected in submandibular glands by immunohistochemistry or by polymerase chain reaction. In addition, retroviral particles were secreted into the lumen of exocrine ducts of submandibular glands.


CONCLUSIONS
This might be an SS animal model that is induced by a certain defined retrovirus. This experimental system might provide us with valuable information for analyzing the mechanisms of how a retrovirus could induce SS.
Suzuki
K
K
Department of Blood Products, National Institute of Health, Tokyo, Japan.
Makino
M
M
Okada
Y
Y
Kinoshita
J
J
Yui
R
R
Kanazawa
H
H
Asakura
H
H
Fujiwara
M
M
Mizuochi
T
T
Komuro
K
K
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D007150:Immunohistochemistry; D007668:Kidney / Q000382:microbiology / Q000473:pathology / Q000648:ultrastructure; D007765:Lacrimal Apparatus / Q000382:microbiology / Q000473:pathology* / Q000648:ultrastructure; D009052:Leukemia Virus, Murine / Q000302:isolation & purification / Q000472:pathogenicity*; D008099:Liver / Q000382:microbiology / Q000473:pathology / Q000648:ultrastructure; D008214:Lymphocytes / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010179:Pancreas / Q000382:microbiology / Q000473:pathology* / Q000648:ultrastructure; D016133:Polymerase Chain Reaction / Q000379:methods; D012859:Sjogren's Syndrome / Q000382:microbiology / Q000473:pathology*; D013363:Submandibular Gland / Q000382:microbiology / Q000473:pathology* / Q000648:ultrastructure; D013961:Thyroid Gland / Q000382:microbiology / Q000473:pathology* / Q000648:ultrastructure
D017931:DNA Primers; D004279:DNA, Viral; D015345:Oligonucleotide Probes