Induction of anti-Forssman antibodies in the hamster-to-rat xenotransplantation model.
BACKGROUND
In the hamster-to-rat heart xenotransplantation model, the serum response of the host contributes to determine whether the xenograft is accommodated or rejected.


METHODS
To further characterize the serum response in this model, we compared anti-hamster antibodies found in naive LEW-1A rats, or in LEW-1A rats rejecting or accommodating a hamster heart, using a combination of cobra venom factor (CVF) and cyclosporin A (CsA) given for 10 days, and then CsA alone.


RESULTS
Hamster hearts grafted into rat recipients contained IgG and IgA deposits to the same extent whether the xenograft was rejected or accommodated. Only immunoglobulins of the IgM isotype were found to be more abundant in recipients rejecting their graft. A significant part of this IgM response was directed toward the Forssman antigen, a sphingolipid present in the hamster but not in the rat. However, although anti-Forssman antibodies bind in situ to hamster tissues, this binding was not able to induce hyperacute rejection after antibody transfer. Furthermore, depletion of anti-Forssman antibodies from a rejecting serum did not modify its rejection properties.


CONCLUSIONS
Unlike the pig-to-primate discordant xenotransplantation model, in which preexisting anti-carbohydrate antibodies are directly responsible for hyperacute rejection, in the concordant hamster-to-rat situation, the evoked IgM anti-Forssman carbohydrate antibodies do not appear to be the main cause of the vascular rejection.
Brouard
S
S
Institut National de la Santé et de la Recherche Médicale-Unité 437, Immunointervention dans les Allo et Xénotransplantations, CHU-HOTEL DIEU, Nantes, France.
Bouhours
D
D
Sébille
F
F
Ménoret
S
S
Soulillou
J P
JP
Vanhove
B
B
D000818:Animals; D000910:Antibodies, Heterophile / Q000276:immunology*; D000917:Antibody Formation; D006224:Cricetinae; D004847:Epithelial Cells / Q000276:immunology; D005577:Forssman Antigen / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology; D007075:Immunoglobulin M / Q000032:analysis; D008214:Lymphocytes / Q000276:immunology; D009206:Myocardium / Q000276:immunology; D051381:Rats; D014183:Transplantation, Heterologous
D000910:Antibodies, Heterophile; D007075:Immunoglobulin M; D005577:Forssman Antigen