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

M. Watanabe, Y. Kashiwakura, N. Kusumi, K. Tamayose, Y. Nasu, A. Nagai, T. Shimada, H. Daida, H. Kumon

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1126-1132
Number of pages7
JournalGene Therapy
Volume12
Issue number14
DOIs
Publication statusPublished - Jul 2005

Keywords

  • Adeno-associated virus
  • Delayed-type hypersensitivity
  • Experimental autoimmune orchitis
  • Interleukin-10
  • Male infertility

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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