Donor‐reactive memory T cells generated via heterologous immunity represent a potent barrier to long‐term graft survival following transplantation because of their increased precursor frequency, rapid effector function, altered trafficking patterns, and reduced reliance on costimulation signals for activation. Thus, the identification of pathways that control memory T cell survival and secondary recall potential may provide new opportunities for therapeutic intervention. Here, we discovered that donor‐specific effector/memory CD8⁺ T cell populations generated via exposure to acute vs latent vs chronic infections contain differential frequencies of CD8⁺ T cells expressing the inhibitory Fc receptor FcγRIIB. Results indicated that frequencies of FcγRIIB‐expressing CD8⁺ donor‐reactive memory T cells inversely correlated with allograft rejection. Furthermore, adoptive T cell transfer of Fcgr2b ^−/− CD8⁺ T cells resulted in an accumulation of donor‐specific CD8⁺ memory T cells and enhanced recall responses, indicating that FcγRIIB functions intrinsically to limit T cell CD8⁺ survival in vivo. Lastly, we show that deletion of FcγRIIB on donor‐specific CD8⁺ memory T cells precipitated costimulation blockade‐resistant rejection. These data therefore identify a novel cell‐intrinsic inhibitory pathway that functions to limit the risk of memory T cell–mediated rejection following transplantation and suggest that therapeutic manipulation of this pathway could improve outcomes in sensitized patients.

中文翻译：

---

CD8+ T 细胞上的 FcγRIIB 表达减轻了记忆 T 细胞介导的排斥反应。

通过异源免疫产生的供体反应性记忆 T 细胞代表了移植后长期移植物存活的强大障碍，因为它们增加了前体频率、快速效应子功能、改变了运输模式，并减少了对共刺激信号的激活依赖。因此，控制记忆 T 细胞存活和二次回忆潜能的途径的鉴定可能为治疗干预提供新的机会。在这里，我们发现通过暴露于急性感染、潜伏感染和慢性感染而产生的供体特异性效应/记忆 CD8 ⁺ T 细胞群包含表达抑制性 Fc 受体 FcγRIIB 的不同频率的 CD8 ^{+ T 细胞。}结果表明，表达 FcγRIIB 的 CD8 ^+的频率供体反应性记忆 T 细胞与同种异体移植排斥反应呈负相关。此外，Fcgr2b ^-/- CD8 ⁺ T 细胞的过继性 T 细胞转移导致供体特异性 CD8 ⁺记忆 T 细胞的积累和增强的回忆反应，表明 FcγRIIB 的内在功能是限制 T 细胞 CD8 ⁺在体内的存活。最后，我们表明在供体特异性 CD8 ^{+上删除 FcγRIIB}记忆 T 细胞沉淀共刺激阻断抗性排斥反应。因此，这些数据确定了一种新的细胞内在抑制途径，该途径的作用是限制移植后记忆 T 细胞介导的排斥反应的风险，并表明对该途径的治疗性操作可以改善致敏患者的预后。