Adeno-associated virus-mediated human IL-10 gene transfer suppresses the development of experimental autoimmune orchitis.
Testicular germ cell-induced autoimmune orchitis is characterized by inflammatory cell infiltration followed by disturbance of spermatogenesis. Experimental autoimmune orchitis (EAO) is an animal model for human immunological male infertility; delayed-type hypersensitivity (DTH) response plays a key role in its induction. Interleukin-10 (IL-10) is a regulatory cytokine that is critical in preventing organ-specific autoimmune inflammation. To determine the effects on EAO of human IL-10 (hIL-10) gene transfer, C3H/He mice immunized by unilateral testicular injury were administered intramuscular (i.m.) injections of adeno-associated viral (AAV) vector-encoding hIL-10 on the day of immunization. Serum hIL-10 was detected beginning at 1 week postinjection, and peaked at 3 weeks. Histological examinations showed a significantly low incidence of orchitis and disturbance of spermatogenesis in AAV hIL-10-treated mice, and the DTH response to autologous testicular cells was significantly suppressed. Immunohistochemical analysis of IFN- and IL-2, T-cell-associated cytokines, in the spleen and testes revealed significantly fewer cytokine-expressing cells after treatment. We conclude that a single i.m. administration of AAV hIL-10 significantly suppresses EAO and hypospermatogenesis by regulating cell-mediated immunity in the testes.
Watanabe
M
M
Department of Urology, Okayama University Graduate school of Medicine and Dentistry, Okayama, Japan.
Kashiwakura
Y
Y
Kusumi
N
N
Tamayose
K
K
Nasu
Y
Y
Nagai
A
A
Shimada
T
T
Daida
H
H
Kumon
H
H
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000517:prevention & control; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009920:Orchitis / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D013091:Spermatogenesis; D013154:Spleen / Q000276:immunology; D013737:Testis / Q000276:immunology
D016207:Cytokines; D016753:Interleukin-10