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Prepublished online as a Blood First Edition Paper on May 29, 2003; DOI 10.1182/blood-2003-03-0759.
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Blood, 15 September 2003, Vol. 102, No. 6, pp. 1943-1950
PLENARY PAPERS
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
From the Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
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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