Research ArticleGraft-Versus-Host Disease

Combined OX40L and mTOR blockade controls effector T cell activation while preserving Treg reconstitution after transplant

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Science Translational Medicine  20 Sep 2017:
Vol. 9, Issue 408, eaan3085
DOI: 10.1126/scitranslmed.aan3085

Tackling T cells in GVHD

Graft-versus-host disease (GVHD) after stem cell transplantation is mediated by effector T cells derived from donor stem cells, but GVHD can also be abrogated by donor-derived regulatory T cells. GVHD prophylaxis ideally should then allow regulatory T cell responses while inhibiting effector T cells. Tkachev et al. now provide very promising results in a nonhuman primate model, which suggest that such therapy is possible. They used mTOR inhibition in combination with OX40L blockade, which resulted in reduced damaging T cell reconstitution but preserved regulatory T cell activity. The combination therapy also led to a considerable survival benefit. These findings support testing of this therapy in patients.