Targeting of B and T lymphocyte associated (BTLA) prevents graft-versus-host disease without global immunosuppression

Jörn C. Albring, Michelle M. Sandau, Aaron S. Rapaport, Brian T. Edelson, Ansuman Satpathy, Mona Mashayekhi, Stephanie K. Lathrop, Chyi Song Hsieh, Matthias Stelljes, Marco Colonna, Theresa L. Murphy, Kenneth M. Murphy

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Graft-versus-host disease (GVHD) causes significant morbidity and mortality in allogeneic hematopoietic stem cell transplantation (aHSCT), preventing its broader application to non-life-threatening diseases. We show that a single administration of a nondepleting monoclonal antibody specific for the coinhibitory immunoglobulin receptor, B and T lymphocyte associated (BTLA), permanently prevented GVHD when administered at the time of aHSCT. Once GVHD was established, anti-BTLA treatment was unable to reverse disease, suggesting that its mechanism occurs early after aHSCT. Anti-BTLA treatment prevented GVHD independently of its ligand, the costimulatory tumor necrosis factor receptor herpesvirus entry mediator (HVEM), and required BTLA expression by donor-derived T cells. Furthermore, anti-BTLA treatment led to the relative inhibition of CD4+ forkhead box P3- (Foxp3-) effector T cell (T eff cell) expansion compared with precommitted naturally occurring donor-derived CD4+ Foxp3+ regulatory T cell (T reg cell) and allowed for graft-versus-tumor (GVT) effects as well as robust responses to pathogens. These results suggest that BTLA agonism rebalances T cell expansion in lymphopenic hosts after aHSCT, thereby preventing GVHD without global immunosuppression. Thus, targeting BTLA with a monoclonal antibody at the initiation of aHSCT therapy might reduce limitations imposed by histocompatibility and allow broader application to treatment of non-life-threatening diseases.

Original languageEnglish
Pages (from-to)2551-2559
Number of pages9
JournalJournal of Experimental Medicine
Volume207
Issue number12
DOIs
StatePublished - Nov 22 2010

Fingerprint

Dive into the research topics of 'Targeting of B and T lymphocyte associated (BTLA) prevents graft-versus-host disease without global immunosuppression'. Together they form a unique fingerprint.

Cite this