*Purpose: The interactions between CD80 and CD86 on antigen-presenting cells and CD28 on T cells may play an important role in alloimmune responses. We investigated the effects of blocking antibodies to CD80 and CD86 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 were received 250μg/day of anti-CD80 antibody (RM80) and anti-CD86 antibody (GL-1) from the day of transplantation to 2 days afterward. Histologic studies were performed to determine whether the graft structure of the cardiac allografts was preserved on day 30. Flow cytometry studies were performed to determine whether CD4⁺CD25⁺Foxp3⁺ regulatory T cells were generated and donor specific antibody (DSA) was suppressed on day 30. Adoptive transfer of CD4⁺ and CD4⁺CD25⁺ splenocytes were performed to determine whether CD4⁺ and CD4⁺CD25⁺ cells were involved with the graft prolongation and DSA suppression.

*Results: Untreated CBA recipients rejected C57BL/6 cardiac grafts acutely (median survival time [MST], 7 days). CBA recipients treated with RM80 and GL-1 significantly prolonged allograft survival (MST, >100 days). Histologic studies showed that myocardial damage of allografts in RM80/GL-1-treated CBA recipients was suppressed, compared with those in untreated recipients. Flow cytometry studies showed CD4⁺ and CD4⁺CD25⁺Foxp3⁺ cells in splenocytes from RM80/GL-1-treated recipients were not increased, but DSA production was suppressed. Adoptive transfer of CD4⁺CD25⁺ splenocytes from RM80/GL-1-treated primary recipients could not prolong allograft survival in the secondary recipients. On the other hand, Adoptive transfer of CD4⁺ splenocytes from RM80/GL-1-treated primary recipients could prolong allograft survival in the secondary recipients and DSA was suppressed on day 7 after adoptive transfer.

*Conclusions: Blocking anti-CD80 and CD86 antibodies could suppressed DSA, which may be driven through anergy CD4⁺ cells.

« Back to 2022 American Transplant Congress