| Autor: |
Page, E.K., Page, A.J., Kwun, J., Gibby, A.C., Leopardi, F., Jenkins, J.B., Strobert, E.A., Song, M., Hennigar, R.A., Iwakoshi, N., Knechtle, S.J. |
| Zdroj: |
American journal of transplantation; September 2012, Vol. 12 Issue: 9 p2395-2405, 11p |
| Abstrakt: |
Chronic allograft rejection is a major impediment to long-term transplant success. Humoral immune responses to alloantigens are a growing clinical problem in transplantation, with mounting evidence associating alloantibodies with the development of chronic rejection. Nearly a third of transplant recipients develop de novoantibodies, for which no established therapies are effective at preventing or eliminating, highlighting the need for a nonhuman primate model of antibody-mediated rejection. In this report, we demonstrate that depletion using anti-CD3 immunotoxin (IT) combined with maintenance immunosuppression that included tacrolimus with or without alefacept reliably prolonged renal allograft survival in rhesus monkeys. In these animals, a preferential skewing toward CD4 repopulation and proliferation was observed, particularly with the addition of alefacept. Furthermore, alefacept-treated animals demonstrated increased alloantibody production (100%) and morphologic features of antibody-mediated injury. In vitro, alefacept was found to enhance CD4 effector memory T cell proliferation. In conclusion, alefacept administration after depletion and with tacrolimus promotes a CD4+memory T cell and alloantibody response, with morphologic changes reflecting antibody-mediated allograft injury. Early and consistent de novoalloantibody production with associated histological changes makes this nonhuman primate model an attractive candidate for evaluating targeted therapeutics. |
| Databáze: |
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