Experimental autoimmune vesiculo-prostatitis (EAVP) was transferred within inbred Wistar rats by a relatively small number of spleen cells obtained 30 days after immunization of donors with MAG extract in CFA and injected in the internal jugular vein of recipients. Specific tissue alterations identical to those present in the glands of the donors were observed 7 days after the transfer of the cells. The main alteration present was infiltration of mononuclear cells in the interstitium accompanied by fibrosis in more severe cases and flattening of epithelium in the ventral and dorsal prostate, seminal vesicle, and occasionally in coagulating gland. Nine out of ten recipients developed sexual accessory glandular lesions of various degrees. No histological alterations were observed in the absence of cell-mediated immune response and extensive damage was only observed in rats expressing two or more positive assays. The separation of the transferred cells into enriched population of T and B cells has proved that T lymphocytes are required for the production of the tissue lesions. Depletion of T lymphocytes by nylon wool separation and anti-rat thymocytes serum and complement completely abrogate their capacity to transfer the glandular alterations. Furthermore, specific antibody precursor cells on their own seem to be incapable to promote the antibody synthesis and to initiate the glandular damage. We conclude that T lymphocytes are required for the adoptive transfer of specific tissue damage observed in autoimmune vesiculo-prostatitis as well as for the development of a cell-mediated immune response to MAG antigens. Whether the same or distinct T-cell subsets are involved in these two effects is discussed.

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)

Isoimmunization of Wistar rats with male accessory gland (MAG) extract and complete Freund's adjuvant (CFA) induces a specific cell‐mediated immune response detected by skin delayed hypersensitivity, spleen lymphocyte culture as well as by the presence of macrophage inhibitory factor and skin reactive factor. Specific antibodies have also been investigated by hemagglutination, immunodiffusion, and complement‐fixation tests. In a group of rats receiving a single immunizing dose no antibody response was detected, but in 5 out of 8 rats a cell‐mediated immune response was found accompanied in three of them by mild histological changes in the target organ. In a second group that underwent a more intense and extended immunization schedule, the humoral response was detected by complement fixation in only three undiluted sera. The cellular immune mechanism was found in 18 out of 20 rats through one or more of the tests in the study. Male accessory gland lesions in various degrees were observed in 15 cases and they were mainly represented by mononuclear infiltration. Whether a cell‐mediated or humoral mechanism is responsible for induction of the tissue damage observed in the target glands is discussed.

Spleen cells obtained 30 days after the first immunization of rats isoimmunized with an extract of male accessory glands (MAG) were capable of adoptively transferring specific cell-mediated immunity to normal syngenic recipients. Humoral and cell-mediated immune responses were investigated in donor and in the recipient rats that were killed 7 days after intravenous (IV) injection of the cells. In recipient rats the cell-mediated immunity showed multiple ways of expression and in some cases this was exemplified by a sharp increase in regard to the donor's response. Furthermore, a widespread reactivity in the spleen, lymph nodes, and thymus cells was detected. On the contrary, no circulating antibodies to MAG antigens were demonstrated after the spleen cell transfer. Cell separation studies showed that a nylon wool-nonadherent cell was responsible for the transfer of the cell-mediated immune response. This was abrogated by depletion of T lymphocytes and treatment with antirat thymocytes serum and complement. The mechanism of transfer and development of the cell-mediated immunity in recipient rats is discussed.

A correlation between spleen B-cell antibody production against MAG antigens and the presence of different antibodies in circulation or antibodies bound to target glands was attempted. The number of 7S and 19S Ig-secreting cells (ISC) found in the spleen and the number of ISC generated after in vitro stimulation of the cells with MAG antigens were evaluated by using the hemolytic plaque assay. Low numbers of 7S and 19S ISC--less than 0.01% of spleen cells--were generated in response to MAG immunization, and no significative increase was observed after in vitro culture of spleen cells with MAG antigens, suggesting that secretory activity of the B-cells can not be improved when liberated from humoral homeostatic mechanisms. The humoral response of MAG-immunized rats, investigated by complement fixation and immunodiffusion assays, has proved negative, and in only two out of 17 rats a weak haemagglutinating activity was observed. Attempts to detect antibodies bound to cellular MAG antigens by immunofluorescence have shown a weak fluorescence in the epithelial cells of the prostate gland in only two rats. In both cases a concomitant tissue damage was observed, but in nine out of 11 cases with histological alterations no fluorescence was observed in the target glands. The medium value of rosette-forming cells (RFC) found in the spleen of MAG-immunized rats did not significantly differ from the value of the HSA-treated control group, although both groups differ in their specific humoral response.(ABSTRACT TRUNCATED AT 250 WORDS)