Research ArticleTransplantation

Aldehyde Dehydrogenase Expression Drives Human Regulatory T Cell Resistance to Posttransplantation Cyclophosphamide

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Science Translational Medicine  13 Nov 2013:
Vol. 5, Issue 211, pp. 211ra157
DOI: 10.1126/scitranslmed.3006960

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Taming Graft-Versus-Host Disease

Allogeneic bone marrow transplant is a curative therapy for many different diseases of the blood. Yet, the transplanted cells have a wild side—they sometimes can attack the recipient, causing graft-versus-host disease (GVHD). One way of preventing GVHD is with posttransplant cyclophosphamide, but what exactly cyclophosphamide does to the reactive T cells remains unclear. Now, Kanakry et al. report that regulatory T cells (Tregs) may play a critical role in this process.

The authors observed that although cyclophosphamide treatment decreased conventional T cell numbers in patients, memory Tregs were relatively preserved. Tregs recovered faster than conventional T cells after therapy, in part due to the protective expression of aldehyde dehydrogenase (ALDH). Indeed, blocking ALDH in cultured cells sensitized Tregs to cyclophosphamide treatment. Moreover, in a xenograft model, removing Tregs prevented the protective effect of cyclophosphamide after transplant. These data provide insight into the mechanistic underpinnings of Tregs in transplant recipients.

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