Indefinite Survival of Fully MHC-Mismatched Murine Cardiac Allografts by Combination of Anti-BTLA mAb (6B2) and Anti-PD-1 mAb (PIM-2).
1Surgery, Teikyo University, Tokyo, Japan
2Cardiovascular Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China
3Cardiovascular Surgery, Teikyo University, Tokyo, Japan
4Thoracic Surgery, The 3rd Affiliated Hospital of Harbin Medical University, Harbin, China
5Immunology, Juntendo University Hospital, Tokyo, Japan.
Meeting: 2016 American Transplant Congress
Abstract number: B27
Keywords: Graft survival, Heart/lung transplantation, Tolerance
Session Information
Session Name: Poster Session B: Allograft Rejection, Tolerance, and Xenotransplantation
Session Type: Poster Session
Date: Sunday, June 12, 2016
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
Background: The co-inhibitory receptor B and T lymphocyte attenuator (BTLA) and Programmed death (PD)-1 had been suggested to have immunomodulatory activity. This study investigated the effect of combination of anti-BTLA monoclonal antibody (mAb) (6B2) and anti-PD-1 mAb (PIM-2) on alloimmune responses in a murine model of cardiac allograft transplantation.
Methods: CBA male mice underwent transplantation of C57BL/6(B6) hearts and received a single dose (100[mu]g) of 6B2 on the day of transplantation (day 0) or four doses on day 0, 3, 6 and 9. Moreover, CBA recipients were also given one dose of combination of 6B2 and PIM-2 on day 0. Adoptive transfer was performed to determine whether regulatory cells were generated. Cell-proliferation, cytokine assessments and HE staining were also performed.
Result: CBA recipients with no treatment rejected B6 cardiac graft acutely (median survival time [MST], 7 days).CBA mice treated with one dose of 6B2 and PIM-2 prolonged allograft survival (MSTs, 46 and 25 days, respectively). Moreover, when CBA mice were given one dose of combination of 6B2 and PIM-2, the allograft survival was indefinitely prolonged (MST, >100 days). Secondary CBA recipients showed prolonged survival of B6 hearts after treatments with whole splenocytes from primary combination-treated CBA recipients carrying B6 cardiac allografts for 30 days (MST, >30 days). Proliferation of splenocytes and interferon-γ production were suppressed and interleukin-4 production was increased in combination-treated mice. HE staining showed that cardiac allografts from primary combination-treated CBA recipients had sparse cell infiltration and only slight myocardial damage.
Conclusion: Combination of anti-BTLA mAb (6B2) and anti-PD-1 mAb (PIM-2) could induce hyporesponsiveness of fully MHC-mismatched cardiac allografts and generate regulatory cells.
CITATION INFORMATION: Yin E, Uchiyama M, Jin X, Shimokawa T, Yagita H, Niimi M. Indefinite Survival of Fully MHC-Mismatched Murine Cardiac Allografts by Combination of Anti-BTLA mAb (6B2) and Anti-PD-1 mAb (PIM-2). Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:
Yin E, Uchiyama M, Jin X, Shimokawa T, Yagita H, Niimi M. Indefinite Survival of Fully MHC-Mismatched Murine Cardiac Allografts by Combination of Anti-BTLA mAb (6B2) and Anti-PD-1 mAb (PIM-2). [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/indefinite-survival-of-fully-mhc-mismatched-murine-cardiac-allografts-by-combination-of-anti-btla-mab-6b2-and-anti-pd-1-mab-pim-2-2/. Accessed May 9, 2025.« Back to 2016 American Transplant Congress