Anti-CD3 F(ab')2 Prevents Graft-Versus-Host Disease by Selectively Depleting Donor T Cells Activated by Recipient Alloantigens1
Xue-Zhong Yu*, Sasha J. Bidwell*, Paul J. Martin*, and Claudio Anasetti2,*,
* Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and Department of Medicine, University of Washington, Seattle, WA 98195
Transplantation tolerance is facilitated by activation-induced apoptosis of peripheral T cells triggered by specific Ag. Abs specific for the nonpolymorphic CD3 component of the TCR complex bind to APCs through Fc-FcR interactions, mimic MHC-peptide, and activate polyclonal T cells. In contrast, F(ab')2 of anti-CD3 Abs do not activate naive T cells but induce apoptosis of Ag-activated, cycling T cells. Here, we report that treatment with anti-CD3 F(ab')2 can selectively induce apoptosis of donor T cells that recognize a recipient alloantigen, thereby preventing graft-vs-host disease initiated by a TCR-transgenic T cell population. The selective elimination of Ag-activated T cells by non-FcR-binding anti-CD3 Abs could serve as an ideal strategy to prevent graft-vs-host disease and allograft rejection or to treat autoimmune disorders. |
