Anti-third-party veto CTLs overcome rejection of hematopoietic allografts: synergism with rapamycin and BM cell dose.

Blood
Esther Bachar-LustigY Reisner

Abstract

Several bone marrow cells and lymphocyte subpopulations, known as "veto cells," were shown to induce transplantation tolerance across major histocompatibility antigens. Some of the most potent veto cells are of T-cell origin, and in particular a very strong veto activity was documented for cytotoxic T-lymphocyte (CTL) lines or clones. However, these cells also possess marked graft-versus-host (GVH) reactivity. In the present study we evaluated a new approach to deplete CTLs of antihost clones by stimulating the donor T cells against third-party stimulators in the absence of exogenous interleukin 2 (IL-2). We demonstrate that such CTLs are depleted of GVH reactivity while maintaining marked veto activity in vitro. Furthermore, marked synergism was exhibited between the veto CTLs and rapamycin when tested in a murine model, which measures T-cell-mediated bone marrow allograft rejection, or in sublethally irradiated allogeneic hosts. Our results suggest that engraftment of early progenitors could be enhanced by using host-nonreactive anti-third-party CTLs, in conjunction with nonmyeloablative rapamycin-based conditioning protocols, thereby significantly reducing the toxicity of allogeneic transplantation.

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Citations

Oct 6, 2007·Immunologic Research·Yair Reisner
Jun 29, 2007·Nature Clinical Practice. Oncology·Ben SprangersAn D Billiau
Apr 5, 2005·Bone Marrow Transplantation·D L Porter, C H June
Jan 20, 2006·Transplantation·Kimberly M Anderson, James C Zimring
Jan 19, 2013·Journal of the American Podiatric Medical Association·Robert G FrykbergArthur Tallis
Jun 7, 2014·Current Opinion in Organ Transplantation·Noga Or-Geva, Yair Reisner
Aug 8, 2008·Current Opinion in Organ Transplantation·Anna Valujskikh
Jan 18, 2011·Hematology/oncology Clinics of North America·David Hagin, Yair Reisner
Feb 2, 2010·Immunology and Allergy Clinics of North America·David Hagin, Yair Reisner
Jan 20, 2009·International Immunopharmacology·Eran Ophir, Yair Reisner
Oct 13, 2007·Blood Cells, Molecules & Diseases·Maria De IoanniAntonio Tabilio
Jun 17, 2005·Annals of the New York Academy of Sciences·Yair ReisnerEsther Bachar-Lustig
Nov 6, 2004·Blood Cells, Molecules & Diseases·Yair ReisnerEsther Bachar-Lustig
Jun 4, 2015·Bone Marrow Transplantation·N Or-Geva, Y Reisner
Jun 21, 2007·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Seitaro TerakuraKoji Kato
Aug 21, 2004·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Andreas A ErdmannDaniel H Fowler
Aug 3, 2017·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Rumi IshiiKazunari Tanabe
Aug 23, 2019·Bone Marrow Transplantation·Rakefet Sidlik-Muskatel, Yair Reisner
Jul 15, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Assaf LaskYair Reisner
Dec 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jacopo MariottiDaniel H Fowler
Nov 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shlomit Reich-ZeligerYair Reisner
Nov 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shlomit Reich-ZeligerYair Reisner

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