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Prepublished online as a Blood First Edition Paper on May 29, 2003; DOI 10.1182/blood-2003-03-0759.

Submitted March 11, 2003
Accepted May 16, 2003
Anti-third party veto CTLs overcome rejection of hematopoietic allografts: synergism with rapamycin and BM cell dose
Esther Bachar-Lustig, Shlomit Reich-Zeliger, and Yair Reisner*
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
* Corresponding author; email: yair.reisner{at}weizmann.ac.il.
Several bone marrow cells and lymphocyte subpopulations, known as 'veto cells', were shown to induce transplantation tolerance across major histocompatbility antigens. Some of the most potent veto cells are of T cell origin, and in particular a very strong veto activity was documented for CTL lines or clones. However, these cells also possess marked GVH reactivity. In the present study we evaluated a new approach to deplete CTLs of anti-host clones by stimulating the donor T cells against third party stimulators in the absence of exogenous 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 non-reactive anti-third party CTLs, in conjunction with non-myeloablative rapamycin based conditioning protocols, thereby significantly reducing the toxicity of allogeneic transplantation.

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