Background: The co-inhibitory receptor B and T lymphocyte attenuator (BTLA; CD272) has been implicated in the regulation of autoimmune and may potentially play an important role in alloimmune responses. We investigated the effect of anti-BTLA monoclonal antibody (6B2) in the survival of fully MHC-mismatched murine cardiac allograft transplantation.

Methods: CBA mice (H2^k) underwent transplantation of C57BL/6 (B6, H2^b) hearts and received a single dose of anti-BTLA monoclonal antibody (6B2) by intraperitoneal injection on the day of transplantation and for 3rd, 6th and 9th day thereafter. Adoptive transfer study, flow cytometry study and immunohistochemical (IHC) study were performed to determine whether Foxp3⁺ regulatory T cells were generated. Histologic, cell-proliferation and cytokine assessments were performed.

Result: Untreated CBA mice rejected B6 cardiac grafts acutely (median survival time [MST], 7 days). When CBA mice were treated with 6B2 on the day of transplantation and for 3rd, 6th and 9th day thereafter, the allograft survival was significantly prolonged to MST, >100 days and had more Foxp3⁺ cell in IHC study.Secondary CBA recipients given whole splenocytes from primary 6B2-treated CBA recipients with B6 cardiac allografts 30 days after grafting had prolonged B6 allograft survival (MST, >30 days).Cell proliferation of splenocytes was suppressed in 6B2-treated mice compared to that from splenocytes of untreated recipients. Flow cytometry studies showed an increased CD4⁺CD25⁺Foxp3⁺ cell population in splenocytes from 6B2-treated mice. HE staining showed that cardiac allografts from primary 6B2-treated CBA recipients had sparse cell infiltration and only slight myocardial damage.

Conclusion: Anti-BTLA monoclonal antibody (6B2) could induce hyporesponsiveness of fully MHC-mismatched cardiac allografts and generation of CD4⁺CD25⁺Foxp3⁺ regulatory T cells.

CITATION INFORMATION: Uchiyama M, Yin E, Jin X, Shimokawa T, Yagita H, Niimi M. Anti-BTLA Antibody (6B2) Induced Prolongation of Fully MHC-Mismatched Murine Cardiac Allograft and Generation of Foxp3+ Regulatory T Cells. Am J Transplant. 2016;16 (suppl 3).

« Back to 2016 American Transplant Congress