An aberrant prostate antigen–specific immune response causes prostatitis in mice and is associated with chronic prostatitis in humans
Yafei Hou, … , Mark S. Anderson, Lawrence Fong
Yafei Hou, … , Mark S. Anderson, Lawrence Fong
Published June 1, 2009
Citation Information: J Clin Invest. 2009;119(7):2031-2041. https://doi.org/10.1172/JCI38332.
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Research Article Immunology

An aberrant prostate antigen–specific immune response causes prostatitis in mice and is associated with chronic prostatitis in humans

Abstract

Chronic prostatitis is a common disease of unclear etiology and has no specific treatment. Mice deficient in the expression of the autoimmune regulator (Aire) gene, which are defective in thymic expression of self antigens and central tolerance, develop spontaneous prostatitis. In this study, we found that Aire-deficient mice developed spontaneous B and T cell immune responses to a prostate autoantigen, seminal vesicle secretory protein 2 (SVS2), which we believe to be novel. We show that thymic expression of this self antigen was Aire dependent. Moreover, prostatitis was induced in WT mice through immunization with SVS2, demonstrating that immunity to SVS2 was sufficient to induce prostatitis. The clinical relevance of this antigen was highlighted by our observation that patients with chronic prostatitis possessed specific autoantibodies against the human SVS2-like seminal vesicle protein semenogelin. These results provide direct evidence that spontaneous chronic prostatitis is an autoimmune disease and is regulated by both central and peripheral tolerance. Moreover, SVS2 and semenogelin are among the relevant autoantigens in mice and humans, respectively.

Authors

Yafei Hou, Jason DeVoss, Vinh Dao, Serena Kwek, Jeffrey P. Simko, Douglas G. McNeel, Mark S. Anderson, Lawrence Fong

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Figure 4

Spontaneous T cell responses to SVS2 in Aire-KO mice.

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Spontaneous T cell responses to SVS2 in Aire-KO mice. (A) Splenocyte...
(A) Splenocytes derived from Aire-KO B6 mice were depleted of CD4+ or CD8+ T cells or of CD19+ B cells by FACS. Sorted cells (5 × 106 cells) were adoptively transferred into male RAG-KO B6 mice. H&E staining of representative frozen prostate sections demonstrate that cells depleted of CD8+ T cells and CD19+ B cells, but not CD4+ T cells, were capable of transferring disease into RAG-KO mice. Results are representative of 2 separate adoptive transfer experiments, each with 2 mice per group. Scale bars: 150 μm. (B) Splenocytes (200,000 per well) from Aire-KO and WT mice were assessed for T cell responses against MBP-SVS2 (10 μg/ml) or MBP (10 μg/ml) by IFN-γ ELISPOT. Values are mean ± SD. SFU, spot-forming unit. (C) Results from individual Aire-KO and WT mice (n = 7 per group) of the experiment described in B. (D) IFN-γ ELISPOT assays were also performed with purified semen-derived SVS2 (10 μg/ml) and OVA (10 μg/ml) (n = 5 per group). In C and D, data points represent individual mice, horizontal bars denote means, and significance of differences was assessed by 2-tailed Student’s t test.