Combined costimulatory and leukocyte functional antigen-1 blockade prevents transplant rejection mediated by heterologous immune memory alloresponses.

摘要: BACKGROUND Recent evidence suggests that alloreactive memory T cells are generated by the process of heterologous immunity, whereby arising in response to pathogen infection crossreact with donor antigens. Because their diminished requirements for costimulation during recall, these pathogen-elicited allocrossreactive particular clinical importance, especially given emergence costimulatory blockade as a transplant immunosuppression strategy. METHODS We used an established model immunity involving sequential naive C57BL/6 recipient lymphocytic choriomeningitis virus and vaccinia virus, followed combined skin bone marrow from BALB/c donor. RESULTS demonstrate coupling integrin antagonist anti-leukocyte functional antigen (LFA)-1 could surmount barrier posed fully allogeneic murine system. The regimen suppressed proliferation attenuated cytokine effector responses. This also promoted retention FoxP³⁺ Tregs draining lymph nodes. Finally, we show vitro mixed lymphocyte reaction system using human cells, combination belatacept anti-LFA-1 was able suppress production resistant alone. CONCLUSIONS As against LFA-1 exists has been clinically treat psoriasis, findings have significant translational potential future trials.