Establishment of a concordant xenogeneic splenocyte injection model for the dynamic study of the marginal zone in the spleen.
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.


CONCLUSIONS
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.
Yasutomi
M
M
Department of Surgery II, Nagoya University School of Medicine, Japan.
Ito
M
M
Hayashi
S
S
Ohtsuka
S
S
Namii
Y
Y
Uchida
K
K
Yokoyama
I
I
Takagi
H
H
D000818:Animals; D000910:Antibodies, Heterophile / Q000378:metabolism; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects / Q000276:immunology; D017690:Cell Transplantation; D006224:Cricetinae; D003520:Cyclophosphamide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000166:cytology* / Q000276:immunology / Q000473:pathology; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000473:pathology; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D000910:Antibodies, Heterophile; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide