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Cyclophosphamide, but not CTLA4Ig, prolongs survival of fetal pig islet grafts in anti‐T cell monoclonal antibody‐treated NOD mice

Cyclophosphamide, but not CTLA4Ig, prolongs survival of fetal pig islet grafts in anti‐T cell... Abstract: Fetal pig islets, xenografted after organ culture into non‐immunosuppressed prediabetic NOD mice, are rejected within 10 days. Immunosuppression with anti‐T cell (anti‐CD4 and anti‐CD3) monoclonal antibodies alone is highly effective in delaying graft rejection in this discordant model, but rejection eventually occurs, usually within 80 days, despite marked depletion of T cells. In an attempt to prevent rejection, we used cyclophosphamide (CP), a powerful anti‐B cell agent, or CTL4Ig, an inhibitor of T‐cell co‐stimulation (via B7–1 (CD80) and B7–2 (CD86)), either given in combination with anti‐CD4 (GK1.5) or anti‐CD3 (KT3) MAb to the recipient mice. The addition of cyclophosphamide in a dose that significantly depleted B cells in peripheral blood was highly effective in preventing rejection, with xenografts surviving for at least 112 days, when the experiment was terminated. CTLA4Ig, administered alone, did not prevent delayed rejection (rejection occurred in <60 days) and, in contrast to CP, did not prevent delayed rejection when used in combination with GK1.5 and KT3 treatment. Thus, immunosuppressive agents found to be highly effective in other strains, e.g., CTLA4Ig and anti‐T cell MAbs, had a lesser effect in NOD mice but the addition of an anti‐B cell drug, CP, was useful. This finding may be applicable to patients with IDDM. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Xenotransplantation Wiley

Cyclophosphamide, but not CTLA4Ig, prolongs survival of fetal pig islet grafts in anti‐T cell monoclonal antibody‐treated NOD mice

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References (22)

Publisher
Wiley
Copyright
Copyright © 1998 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0908-665X
eISSN
1399-3089
DOI
10.1111/j.1399-3089.1998.tb00030.x
Publisher site
See Article on Publisher Site

Abstract

Abstract: Fetal pig islets, xenografted after organ culture into non‐immunosuppressed prediabetic NOD mice, are rejected within 10 days. Immunosuppression with anti‐T cell (anti‐CD4 and anti‐CD3) monoclonal antibodies alone is highly effective in delaying graft rejection in this discordant model, but rejection eventually occurs, usually within 80 days, despite marked depletion of T cells. In an attempt to prevent rejection, we used cyclophosphamide (CP), a powerful anti‐B cell agent, or CTL4Ig, an inhibitor of T‐cell co‐stimulation (via B7–1 (CD80) and B7–2 (CD86)), either given in combination with anti‐CD4 (GK1.5) or anti‐CD3 (KT3) MAb to the recipient mice. The addition of cyclophosphamide in a dose that significantly depleted B cells in peripheral blood was highly effective in preventing rejection, with xenografts surviving for at least 112 days, when the experiment was terminated. CTLA4Ig, administered alone, did not prevent delayed rejection (rejection occurred in <60 days) and, in contrast to CP, did not prevent delayed rejection when used in combination with GK1.5 and KT3 treatment. Thus, immunosuppressive agents found to be highly effective in other strains, e.g., CTLA4Ig and anti‐T cell MAbs, had a lesser effect in NOD mice but the addition of an anti‐B cell drug, CP, was useful. This finding may be applicable to patients with IDDM.

Journal

XenotransplantationWiley

Published: Aug 1, 1998

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