An inducible model of abacterial prostatitis induces antigen specific inflammatory and proliferative changes in the murine prostate

Abstract

Prostatitis is a poorly understood disease and increasing evidence suggests inflammation is involved in other prostatic diseases including prostate cancer. The ability of pre-activated CD8 T cells to induce prostatitis was examined by adoptive transfer of prostate antigen specific CD8 T cells into POET-3 mice or POET-3/Luc/Pten(-/+) mice. Characterization of the inflammatory response was determined by examining leukocyte infiltration by histological analysis, flow cytometry and by evaluating cytokine and chemokine levels in prostate tissue. The impact of inflammation on the prostate was evaluated by monitoring epithelial cell proliferation over time. Initiation of inflammation by ovalbumin specific CD8⁺ T cells (OT-I cells) resulted in development of acute prostatitis in the anterior, dorsolateral and ventral prostate of POET-3 and POET-3/Luc/Pten(-/+) mice. Acute prostatitis was characterized by recruitment of adoptively transferred OT-I cells and importantly, autologous CD4⁺ and CD8⁺ T cells, myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg). In concert with leukocyte infiltration elevated levels of pro-inflammatory cytokines and chemokines were observed. Inflammation also resulted in marked epithelial cell proliferation that was sustained up to 80 days post adoptive transfer of OT-I cells. The POET-3 model represents a novel mouse model to study both acute and chronic prostate inflammation in an antigen-specific system. Further, the POET-3 mouse model can be crossed with other genetic models of disease such as the C57/Luc/Pten(-/-) model of prostate cancer, allowing the impact of prostatitis on other prostatic diseases to be evaluated.