Sepsis reduces the number and function of memory CD8 T cells within the host, contributing to the long-lasting state of immunoparalysis. Interestingly, the relative susceptibility of memory CD8 T cell subsets to quantitative/qualitative changes differ after cecal ligation and puncture (CLP)–induced sepsis. Compared with circulatory memory CD8 T cells (T_CIRCM), moderate sepsis (0–10% mortality) does not result in numerical decline of CD8 tissue-resident memory T cells (T_RM), which retain their “sensing and alarm” IFN-γ–mediated effector function. To interrogate this biologically important dichotomy, vaccinia virus–immune C57BL/6 (B6) mice containing CD8 T_CIRCM and skin T_RM underwent moderate or severe (∼50% mortality) sepsis. Severe sepsis led to increased morbidity and mortality characterized by increased inflammation compared with moderate CLP or sham controls. Severe CLP mice also displayed increased vascular permeability in the ears. Interestingly, skin CD103⁺ CD8 T_RM, detected by i.v. exclusion or two-photon microscopy, underwent apoptosis and subsequent numerical loss following severe sepsis, which was not observed in mice that experienced moderate CLP or sham surgeries. Consequently, severe septic mice showed diminished CD8 T cell–mediated protection to localized skin reinfection. Finally, the relationship between severity of sepsis and demise in circulatory versus tissue-embedded memory CD8 T cell populations was confirmed by examining tumor-infiltrating and nonspecific CD8 T cells in B16 melanoma tumors. Thus, sepsis can differentially affect the presence and function of Ag-specific CD8 T cells that reside inside tissues/tumors depending on the severity of the insult, a notion with direct relevance to sepsis survivors and their ability to mount protective memory CD8 T cell–dependent responses to localized Ag re-encounter.

脓毒症减少了宿主内记忆 CD8 T 细胞的数量和功能，导致免疫麻痹的长期状态。有趣的是，在盲肠结扎和穿刺 (CLP) 诱导的败血症后，记忆 CD8 T 细胞亚群对定量/定性变化的相对敏感性不同。用循环存储器的CD8 T细胞（T相比_CIRCM），中度败血症（0-10％死亡率）不会导致CD8组织驻留记忆T细胞（T的数值下降_RM），其保留其“感测和报警” IFN- γ介导的效应子功能。为了探究这种生物学上重要的二分法，痘苗病毒免疫 C57BL/6 (B6) 小鼠含有 CD8 T _CIRCM和皮肤 T _RM患有中度或重度（约 50% 死亡率）败血症。与中度 CLP 或假对照相比，严重脓毒症导致发病率和死亡率增加，特征是炎症增加。严重的 CLP 小鼠的耳朵血管通透性也增加。有趣的是，皮肤CD103 ⁺ CD8 T _RM通过 iv 排除或双光子显微镜检测到的 ，在严重败血症后经历细胞凋亡和随后的数值损失，这在经历中度 CLP 或假手术的小鼠中未观察到。因此，严重的脓毒症小鼠对局部皮肤再感染的 CD8 T 细胞介导的保护作用减弱。最后，通过检查 B16 黑色素瘤肿瘤中的肿瘤浸润和非特异性 CD8 T 细胞，证实了循环系统与组织嵌入记忆 CD8 T 细胞群中败血症的严重程度和死亡之间的关系。因此，脓毒症可以根据损伤的严重程度不同地影响存在于组织/肿瘤内的 Ag 特异性 CD8 T 细胞的存在和功能，