CD27 is required for protective lytic EBV antigen–specific CD8+ T-cell expansion
Yun Deng, Bithi Chatterjee, Kyra D. Zens, Hana Zdimerova, Anne Müller, Patrick Schuhmachers, Laure‐Anne Ligeon, Antonino Bongiovanni, Riccarda Capaul, Andrea Zbinden, Angelika Holler, Hans J. Stauss, Wolfgang Hammerschmidt, Christian Münz
Abstract
Primary immunodeficiencies in the costimulatory molecule CD27 and its ligand, CD70, predispose for pathologies of uncontrolled Epstein-Barr virus (EBV) infection in nearly all affected patients. We demonstrate that both depletion of CD27+ cells and antibody blocking of CD27 interaction with CD70 cause uncontrolled EBV infection in mice with reconstituted human immune system components. While overall CD8+ T-cell expansion and composition are unaltered after antibody blocking of CD27, only some EBV-specific CD8+ T-cell responses, exemplified by early lytic EBV antigen BMLF1-specific CD8+ T cells, are inhibited in their proliferation and killing of EBV-transformed B cells. This suggests that CD27 is not required for all CD8+ T-cell expansions and cytotoxicity but is required for a subset of CD8+ T-cell responses that protect us from EBV pathology.