BACKGROUND: This study was undertaken to establish a simple technique with which we could investigate the relationship between the marginal zone (MZ) in the spleen and antispecies antibody production, as well as to estimate the efficacy of various immunosuppressive treatments in xenotransplantation. METHODS: With a concordant xenogeneic combination (hamster-to-rat), the early phase reaction of the MZ was studied by use of quantitative histologic analysis, and complement-dependent cytotoxic antibody titers were determined in both a heart transplantation model and the splenocyte injection model. Furthermore, changes in the MZ were examined with isogeneic and allogeneic combinations with the splenocyte injection model. Next, the effect of cyclophosphamide, a promising immunosuppressant for concordant xenotransplantation, was examined by use of the splenocyte injection model. RESULTS: With a concordant xenogeneic combination, the MZ enlarged, and antihamster immunoglobulin M antibody synthesis increased after immunization in both models. On the other hand, with an isogeneic combination, the MZ did not expand, and with an allogeneic combination the MZ enlargement was not as great as that with a concordant xenogeneic combination. Cyclophosphamide suppressed the MZ expansion in a dose-dependent manner and effectively diminished antibody production in the splenocyte injection model. CONCLUSION: Dynamic studies of the MZ in the spleen with the splenocyte injection model are useful for the elucidation of the mechanisms of reaction and for estimating the efficacy of various immunosuppressive treatments in concordant xenotransplantation.
BACKGROUND: This study was undertaken to establish a simple technique with which we could investigate the relationship between the marginal zone (MZ) in the spleen and antispecies antibody production, as well as to estimate the efficacy of various immunosuppressive treatments in xenotransplantation. METHODS: With a concordant xenogeneic combination (hamster-to-rat), the early phase reaction of the MZ was studied by use of quantitative histologic analysis, and complement-dependent cytotoxic antibody titers were determined in both a heart transplantation model and the splenocyte injection model. Furthermore, changes in the MZ were examined with isogeneic and allogeneic combinations with the splenocyte injection model. Next, the effect of cyclophosphamide, a promising immunosuppressant for concordant xenotransplantation, was examined by use of the splenocyte injection model. RESULTS: With a concordant xenogeneic combination, the MZ enlarged, and antihamster immunoglobulin M antibody synthesis increased after immunization in both models. On the other hand, with an isogeneic combination, the MZ did not expand, and with an allogeneic combination the MZ enlargement was not as great as that with a concordant xenogeneic combination. Cyclophosphamide suppressed the MZ expansion in a dose-dependent manner and effectively diminished antibody production in the splenocyte injection model. CONCLUSION: Dynamic studies of the MZ in the spleen with the splenocyte injection model are useful for the elucidation of the mechanisms of reaction and for estimating the efficacy of various immunosuppressive treatments in concordant xenotransplantation.