Inhibition of acute cardiac allograft rejection in immunoglobulin-deficient mice

BA Wasowska, Z Qian, E Behrens… - Transplantation …, 1999 - academia.edu
BA Wasowska, Z Qian, E Behrens, D Cangello, F Sanfilippo, WM Baldwin
Transplantation proceedings, 1999academia.edu
NUMEROUS observational and correlative studies sug-gest that alloantibodies may
contribute to acute and chronic rejection. A causative role of antibodies in chronic rejection
has been established in several recent studies in immunodeficient mice. 1–3 The present
study establishes that total elimination of alloantibody responses inhibits acute cardiac
rejection in mice. Untreated wild-type (WT) C57BL/6 (H-2b) mice received cardiac allografts
from two strains of mice: B10. BR (H-2k) and B10. D2 (H-2d). B10. D2 hearts were rejected …
NUMEROUS observational and correlative studies sug-gest that alloantibodies may contribute to acute and chronic rejection. A causative role of antibodies in chronic rejection has been established in several recent studies in immunodeficient mice. 1–3 The present study establishes that total elimination of alloantibody responses inhibits acute cardiac rejection in mice. Untreated wild-type (WT) C57BL/6 (H-2b) mice received cardiac allografts from two strains of mice: B10. BR (H-2k) and B10. D2 (H-2d). B10. D2 hearts were rejected acutely within 13 to 16 days, whereas B10. BR hearts survived 10 to 30 days (n 4 or 5/group). Histologically, acute rejection was characterized by intense cellular infiltration, edema, hemorrhage, and vascular injury. Immunoffuorescence staining of cardiac tissue in WT recipients demonstrated very strong expression of IgM, IgG, and complement (C3) deposition. B10. BR and B10. D2 grafts stimulated strong MHC class I IgM and IgG alloantibody responses as measured by ffow cytometry. In C57BL-Igh-6, Ig knockout (IgKO) mice, at least 50% of B10. BR and B10. D2 hearts survived 100 days, and no alloantibody responses were detected by immunoffuorescence or in the circulation (n 4 or 5/group).
Well-functioning cardiac allografts in IgKO recipients examined 15 days after transplantation showed less vascular damage and less interstitial cell infiltration than transplants in control WT recipients. In summary, the complete elimination of alloantibody responses in C57BL/6 IgKO recipients of B10. BR and B10. D2 cardiac allografts prevents acute cardiac rejection.
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