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Rejection of hamster skin xenografts by rats in the absence of anti‐hamster antibody formation
Author(s) -
Gourlay William A.,
Maki Takashi,
Monaco Anthony P.
Publication year - 1997
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/j.1399-3089.1997.tb00164.x
Subject(s) - hamster , bone marrow , antibody , golden hamster , andrology , titer , antigen , pharmacology , immunology , skin grafting , medicine , biology , surgery
The hamster to rat xenograft combination is considered to be a “difficult” concordant combination. Although the rat lacks preformed anti‐hamster antibodies, there is rapid production of antibodies upon exposure to hamster antigens. When vascularized hamster xenografts are rejected in the rat, anti‐hamster antibodies are invariably detected in both the serum and in the rejected tissue. In allogeneic and other concordant xenogeneic (rat to mouse) combinations, rapamycin has been shown to markedly augment the survival of skin grafts in ALS‐treated, bone marrow injected mice. We investigated the ability of rapamycin to prolong the survival of skin grafts and block antibody production in the hamster to rat combination. Outbred Golden Syrian hamsters served as skin and marrow donors and Lewis rats were recipients. ALS was administered on days ‐1, 0, and +2 relative to skin grafting. Rapamycin was administered at 3 mg/kg on alternate days from day +1 through day +13 (seven doses). Donor specific bone marrow was infused IV on day +4 at a dose of either 100 times 10 6 or 250 times 10 6 nucleated cells. Antibody titers were determined serially by using a complement dependent cytotoxicity assay. The administration of rapamycin alone (MST 8.5 days) and ALS alone (MST 10 days) prolonged graft survival slightly but significantly compared with untreated controls (MST 7 days). The addition of BM had no additional effect on graft survival beyond that achieved with ALS alone. Rapamycin markedly prolonged skin graft survival when added to ALS (MST 16 days), ALS+BM 100 (MST 19 days), or ALS+BM 250 (MST 20.5 days). Rats receiving ALS or ALS+BM produced anti‐hamster antibodies in a slightly delayed fashion and at a slightly lower titer when compared to controls. Treatment with rapamycin alone substantially diminished but did not completely eliminate anti‐hamster antibody production. Rats receiving rapamycin with ALS or ALS+BM failed to produce anti‐hamster antibodies entirely, although they all eventually rejected the hamster skin grafts. Rapamycin, when used in combination with ALS or ALS plus BM is able to prolong skin graft survival and completely abolish antibody production in the hamster to rat combination. The eventual rejection of hamster skin grafts in this circumstance occurs in the absence of anti‐hamster antibodies.