*Purpose: The co-inhibitory receptor B and T lymphocyte attenuator (BTLA; CD272) is a coinhibitory molecule and may play an important role in alloimmune responses. We investigated the effects of agonistic anti-BTLA monoclonal antibody (6B2) on alloimmune responses in a murine model of cardiac allograft transplantation.

*Methods: Fully vascularized heterotopic hearts from C57BL/6 donors were transplanted into CBA mice by using microsurgical techniques. CBA recipients received four doses of 6B2 on day 0, 3, 6 ,9. Adoptive transfer study, flow cytometry study, immunohistochemical (IHC) study, and fluorescent staining study were performed to determine whether the myocardial function in the transplanted cardiac allograft was preserved, CD4⁺CD25⁺Foxp3⁺ regulatory T cells were generated, and donor specific antibody (DSA) was suppressed, respectively.

*Results: CBA recipients exposed with four doses of 6B2 significantly prolonged allograft survival (MST, >100 days). Secondary CBA recipients given whole splenocytes from primary 6B2-exposed CBA recipients with beating B6 cardiac allografts 30 days after transplantation had prolonged B6 allograft survival (MST, >100 days). Additionally, flow cytometry studies show an increased CD4⁺CD25⁺Foxp3⁺ cell population in splenocytes from 6B2-exposed recipients and suppressed DSA on day 30 and 100 after transplantation. However, there were no significant differences in splenic B220+ cell populations between 6B2-exposed and untreated recipients.

*Conclusions: 6B2 could induce the prolongation of fully MHC-mismatched cardiac allograft through an increase of CD4⁺CD25⁺Foxp3⁺ regulatory T cells and consequently the suppression of DSA.

« Back to 2020 American Transplant Congress