The role of veto cells in bone marrow transplantation

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Abstract

Purpose of review

Summarizing and updating new data on the role of veto cells in bone marrow transplantation.

Recent findings

Studies in mice and humans demonstrate that transplantation of hematopoietic progenitors in numbers larger than commonly used (‘megadose’ transplants) overcomes major genetic barriers. In-vitro studies suggest that veto cells, within the population of hematopoietic progenitors, facilitate this favorable outcome. Tolerance induction can be further enhanced by other veto cells. Perhaps the most potent veto cells are CD8+ cytotoxic T lymphocytes. These cells are also associated with marked graft-versus-host disease. Graft-versus-host disease can be separated from the veto activity by several strategies. Alternatively, the use of veto cells of non-T origin can be envisioned for tolerance induction without graft-versus-host disease. The mechanism of action of different veto cells might differ, but two major key molecules, CD8 and FasL, were shown to have a role in several studies, depending on the cell type tested.

Summary

Nonmyeloablative transplants are facilitated by mature T cells in the graft causing more than 20% graft-versus-host disease lethality in HLA-identical patients. The use of veto cells lacking graft-versus-host reactivity might afford a new tool for achieving engraftment of HLA-matched or even mismatched ‘megadose’ purified stem cells.

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