Mechanism by which additional monoclonal antibody (mAB) injections overcome the requirement for thymic irradiation to achieve mixed chimerism in mice receiving bone marrow transplantation after conditioning with anti-T cell mABs and 3-Gy whole body irradiation

Transplantation
Y TomitaMegan Sykes

Abstract

A relatively nontoxic method of conditioning mice has been developed recently that allows allogeneic bone marrow engraftment and specific skin allograft tolerance induction. This regiment included anti-CD4 and anti-CD8 mAbs administered on day -5, followed by 3-Gy whole body irradiation (WBI) and 7-Gy thymic irradiation (TI) on day 0. We have recently shown that the potential toxicity of this regimen can be further reduced by replacing TI with additional anti-T cell mAb injections before and after bone marrow transplantation. Mixed chimerism and prolonged donor-specific skin graft acceptance are induced in 90% of B10 mice conditioned with anti-CD4 and anti-CD8 mAbs on days -6 and -1 and 3-Gy WBI on day 0 without TI, but only in a small fraction of mice receiving a similar regimen, except that mAbs are given on day -5 only. To determine the mechanism of tolerance induction in the former group, we compared the two groups for the extent of thymocyte depletion, for the timing of development of intrathymic and extrathymic chimerism, and for clonal deletion of host-type thymocytes with TCR recognizing superantigens presented by donor class II molecules. The results suggest that administration of a second mAb injection depletes or ina...Continue Reading

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Citations

Jan 1, 1997·Immunologic Research·B Nikolic, M Sykes
Dec 29, 1998·Transplantation Proceedings·M SykesY G Yang
Aug 13, 1998·Transplantation·A N WarrensM Sykes
Sep 9, 2005·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Stephen P Cobbold
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Jun 29, 2007·Microsurgery·Maria Siemionow, Serdar Nasir
Aug 19, 2007·Journal of Internal Medicine·M Sykes
May 5, 2001·Immunity·M Sykes
Feb 13, 2001·Annual Review of Medicine·T Wekerle, M Sykes
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Feb 12, 2017·Stem Cells Translational Medicine·Esma S YolcuNadir Askenasy
May 26, 2001·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·M Sykes, D H Sachs
Aug 23, 2019·Bone Marrow Transplantation·Megan Sykes, Adam D Griesemer

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