Anti-CD137 mAb Deletes Both Donor CD4(+) and CD8(+) T Cells in Acute Graft-versus-host Disease

We previously demonstrated that in vivo engagement of CD137, a member of TNF receptor superfamily, can delete allorective CD4(+) T cells through the induction of activation-induced cell death (AICD) in chronic graft-versus-host disease (cGVHD) and subsequently reverse established cGVHD. In this study, we further showed that agonistic anti-CD137 mAb was highly effective in triggering AICD of donor CD8(+) T cells as well as donor CD4(+) T cells in the C57BL/6→unirradiated (C57BL/6 × DBA/2)F1 acute GVHD model. Our results suggest that strong allostimulation should facilitate AICD of both alloreactive CD4(+) and CD8(+) T cells induced by CD137 stimulation. Therefore, depletion of pathogenic T cells using agonistic anti-CD137 mAb combined with potent TCR stimulation may be used to block autoimmune or inflammatory diseases mediated by T cells.