ISSN:
1365-3083
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
In the present study, we have elucidated the efficacy of two cyclophosphamide (CP)-induced tolerance protocols for the induction of B-cell tolerance against Galα1-3Galβ1-4GlcNAc (αGal) antigens. α1,3-galactosyltransferase-deficient (GalT–/–; H-2b/d) mice received with 1 × 108 AKR (αGal+/+ H-2k) spleen cells (SC) followed by 200 mg/kg CP, or alternatively followed by 200 mg/kg CP, 30 mg/kg Busulfan (BU) and 1 × 108 T-cell-depleted AKR bone marrow cells (BMC). The generation of both anti-αGal and anti-donor antibodies were completely suppressed, but normal antibody production against third party antigens was observed after BALB/c skin grafting in both groups of GalT–/– mice. In GalT–/– mice, treated with SC and CP, mixed chimerism was not observed. Cellular rejection was observed in grafted donor AKR hearts with an absence of humoral rejection, whereas humoral rejection was observed in untreated GalT–/– mice. On the other hand, long-term mixed chimerism and permanent acceptance of donor AKR skin graft and heart graft were achieved in GalT–/– mice treated with SC, CP, BU and BMC. These results demonstrate the efficacy of classical drug-induced tolerance in the induction of B-cell tolerance against αGal antigens. However, induction of stable mixed chimerism was required for the suppression of cellular rejection.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1365-3083.2005.01644.x
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