Regulatory cells suppress GVHD effects of T cells, but allow antitumor activity
The mature donor T cells introduced with bone marrow transplantation (BMT) are capable of killing tumor cells, but they can also cause graft-versus-host disease (GVHD). Now, new study findings identify a regulatory cell that appears to block the GVHD effects, while permitting the antitumor activity.
“The exploitation of such immunosuppressive mechanisms may improve the outcome of clinical BMT and facilitate the successful transplantation from mismatched donors, which could substantially extend the applicability of BMT,” study author Dr. Robert S. Negrin, from Stanford University in California, and colleagues note.The authors’ findings are published in the August 17th online issue of Nature Medicine.Previously, the researchers had shown that donor-derived regulatory cells, known as CD4+CD25+ T cells, were capable of inhibiting lethal GVHD after allogeneic BMT in mice. In the current study, they add to these findings by showing that these cells also allow certain desirable immune effects to occur.The authors studied mice with leukemia and lymphoma that underwent BMT. The regulatory cells suppressed the early expansion of alloreactive donor T cells, thereby reducing the risk of GVHD. In contrast, the cells did not impair antitumor activity, which is largely mediated by the perforin lysis pathway.The findings indicate that “CD4+CD25+ T cells are potent regulatory cells that can separate GVHD from graft-versus-tumor activity mediated by conventional donor T cells,” the authors conclude. (Source: Nat Med 2003;August 17th online issue: Reuters Health: August 22, 2003: Oncolink)