Activation of Cytotoxic Cells by Syngeneic Prostate Antigens in Experimental Autoimmune Vesiculo-Prostatitis

Abstract

In our experimental model of autoimmune vesiculo-prostatitis, obtained by immunization with syngeneic male accessory glands (MAG) and complete Freund's adjuvant, the presence of specific autoreactive cells with cytotoxic activity against prostate antigens was studied. The specific cytotoxicity generated in MAG immunized rats was tested using 51Cr labelled syngeneic prostate cells or labelled chicken erythrocytes coated with specific antigens (MAG homogenate or chromatographic fractions from prostate homogenate) which were used as target cells in a medium free of complement. The addition of spleen sensitized cells to prostate cells suspension produced a significant release of 51Cr in regard to normal effector cells (11.87 +/- SE 1.12 versus 1.5 +/- 0.75). Similar results were obtained when MAG-coated erythrocytes were used as target cells (10.87 +/- SE 0.62 versus 1.50 +/- 0.25). Depletion of T but no B or adherent-cells was shown to abolish the lytic effect indicating that MAG immunization provides determinants which are recognized by sensitized T-cells on cells of the prostate gland where the most severe tissue alterations were previously observed. Erythrocytes coated with chromatographic fractions obtained from prostate homogenate were used to identify the antigens triggering the lytic effect. It was demonstrated that two fractions (FI and FII) functioned as in vivo sensitizing antigens as well as in vitro activating antigens for themselves. The restimulation in vitro of sensitized cells with purified prostate fractions induces an additional lytic effect suggesting that an expansion of effector cells may take place after contacting the antigens at the prostate site.(ABSTRACT TRUNCATED AT 250 WORDS)

Non-obese Diabetic (NOD) Mice are Genetically Susceptible to Experimental Autoimmune Prostatitis (EAP)

“…As in Wistar rats, MAG elicits both a humoral and a cell-mediated response in NOD mice. In the rat model, we have shown that the cell-mediated response gave rise to reactive oxygen intermediates and to CD8 + cytotoxic T cells, two agents potentially capable of causing tissue damage [12,13]. A future objective is to identify which of these effector agents are responsible for the destructive lesions seen in NOD mice and whether B cells and antibodies detected soon after immunization also participate in the pathogenic process.…”

“…EAP can be adoptively transferred into naïve Wistar rats by whole spleen cells of autoimmune donors, but not by spleen cells which have been depleted of T lymphocytes prior to transfer in vitro [11]. Pathogenic reactive oxygen intermediates released by macrophages [12] and cytotoxic T lymphocytes [13] have been demonstrated in diseased rats and may be responsible for tissue alterations observed on histological sections.…”

Experimental rodent models of prostatitis: limitations and potential

“…88 It has been speculated that inflammatory damage induced in this model might be the result of generation of autoreactive cytotoxic cells, increased levels of radical oxidative species from prostatic infiltrating macrophages, and upregulated mast cell degranulation. [89][90][91] These studies do not identify the specific prostatic proteins that are the targets on an immune response. The immunogenicity of prostatic acid phosphatase (PAP) as a target for the induction of an immune response in 6-to 8-week-old Copenhagen rat was investigated by Fong et al 92 They demonstrated that immunization with recombinant rat or human PAP leads to a significant antibody response, 4 weeks after the final boost, but does not generate cytotoxic T lymphocytes (CTL) or result in autoimmune prostatitis.…”

Prostatein or Steroid Binding Protein (PSBP) Induces Experimental Autoimmune Prostatitis (EAP) in NOD Mice

“…Both cytotoxic T lymphocytes and pathogenic reactive oxygen intermediates released by macrophages have been identified in diseased rats and are probably responsible for the tissue alterations observed on histological sections (6,7).…”