Research ArticleGraft-Versus-Host Disease

Human CD8+ Regulatory T Cells Inhibit GVHD and Preserve General Immunity in Humanized Mice

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Science Translational Medicine  16 Jan 2013:
Vol. 5, Issue 168, pp. 168ra9
DOI: 10.1126/scitranslmed.3004943

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Transplanting Hope

Sometimes the treatment is worse than the disease. Therapies for critical illnesses frequently have severe unwanted side effects. One such therapy is bone marrow transplantation (BMT), which is used to treat both malignant and nonmalignant diseases of the blood. Most bone marrow transplants are allogeneic—they are antigenically foreign to the recipient. Thus, immune cells that develop from the transplant recognize the new host—the patient being treated—as “nonself” and attack. This side effect of BMT is called graft-versus-host disease (GVHD) and is controlled by general immunosuppression, which has its own waterfall of negative side effects. Now, Zheng et al. report a way to specifically inhibit GVHD in a humanized mouse model.

The authors transplant CD8hi regulatory T cells (Tregs) into a humanized model of GVHD. They found that these ex vivo–generated CD8hi Tregs reduced GVHD in an allospecific manner while leaving graft versus tumor and general immune responses intact. These cells decreased organ-specific chemokine and cytokine secretion through a mechanism that involved CTLA-4, and, indeed, induced long-term tolerance. If these results can be translated to humans, CD8hi Tregs may prevent the need for long-term general immunosuppression in BMT recipients.