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Adeno-associated virus-mediated human IL-10 gene transfer suppresses the development of experimental autoimmune orchitis

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Abstract

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-γ 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.

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Authors and Affiliations

  1. Department of Urology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan

    M Watanabe, N Kusumi, Y Nasu, A Nagai & H Kumon

  2. Department of Cardiology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan

    Y Kashiwakura & H Daida

  3. Department of Hematology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan

    K Tamayose

  4. Department of Biochemistry and Molecular Biology, Division of Gene Therapy Research, Center for Advanced Medical Technology, Nippon Medical School, Bunkyo-ku, Tokyo, Japan

    T Shimada

Authors
  1. M Watanabe
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  2. Y Kashiwakura
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  3. N Kusumi
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  4. K Tamayose
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  5. Y Nasu
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  6. A Nagai
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  7. T Shimada
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  8. H Daida
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  9. H Kumon
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Appendix A

Appendix A

For transduction efficiency after 48 h incubation with AAV GFP

Table 2 Transduction efficiency after 48 h incubation with AAV GFP
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Watanabe, M., Kashiwakura, Y., Kusumi, N. et al. Adeno-associated virus-mediated human IL-10 gene transfer suppresses the development of experimental autoimmune orchitis. Gene Ther 12, 1126–1132 (2005). https://doi.org/10.1038/sj.gt.3302463

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  • DOI: https://doi.org/10.1038/sj.gt.3302463

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