Solid organ transplantation is the preferred treatment for end-stage organ failure. Although transplant recipients take life-long immunosuppressive drugs, a substantial percentage of them still reject their allografts. Strikingly, barrier organs colonized with microbiota have significantly shorter half-lives than non-barrier transplanted organs, even in immunosuppressed hosts. We previously demonstrated that skin allografts monocolonized with the common human commensal Staphylococcus epidermidis (S.epi) are rejected faster than germ-free (GF) allografts in mice because the presence of S.epi augments the effector alloimmune response locally in the graft. Here, we tested whether host immune responses against graft-resident commensal microbes, including S.epi, can damage colonized grafts independently from the alloresponse. Naive hosts mounted an anticommensal T cell response to colonized, but not GF, syngeneic skin grafts. Whereas naive antigraft commensal T cells modestly damaged colonized syngeneic skin grafts, hosts with prior anticommensal T cell memory mounted a post-transplant immune response against graft-resident commensals that significantly damaged colonized, syngeneic skin grafts. Importantly, allograft recipients harboring this host-versus-commensal immune response resisted immunosuppression. The dual effects of host-versus-commensal and host-versus-allograft responses may partially explain why colonized organs have poorer outcomes than sterile organs in the clinic.

中文翻译：

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宿主对共生免疫反应参与定植实体器官移植的排斥反应

实体器官移植是终末期器官衰竭的首选治疗方法。尽管移植受者终生服用免疫抑制药物，但他们中的很大一部分人仍然排斥他们的同种异体移植物。引人注目的是，即使在免疫抑制的宿主中，微生物群定植的屏障器官的半衰期也明显短于非屏障移植器官。我们之前证明，在小鼠中，与普通人类表皮葡萄球菌( S.epi )单克隆化的皮肤同种异体移植物比无菌 (GF) 同种异体移植物被排斥得更快，因为S.epi的存在增强了移植物局部的效应同种免疫反应。在这里，我们测试了宿主对移植物驻留的共生微生物的免疫反应，包括S.epi，可以独立于同种异体反应损害定植的移植物。天真的宿主对定植的而非 GF 同源皮肤移植物产生反共生 T 细胞反应。虽然幼稚的抗移植共生 T 细胞适度破坏了定植的同基因皮肤移植物，但具有先前反共生 T 细胞记忆的宿主对移植物驻留的共生细胞产生了移植后免疫反应，显着破坏了定植的同基因皮肤移植物。重要的是，携带这种宿主对共生免疫反应的同种异体移植物受体可以抵抗免疫抑制。宿主对共生反应和宿主对同种异体移植物反应的双重影响可能部分解释了为什么在临床上殖民器官的结果比无菌器官差。