Dynamic MAIT Cell Recovery after Severe COVID-19 Is Transient with Signs of Heterogeneous Functional Anomalies.
Dynamic MAIT Cell Recovery after Severe COVID-19 Is Transient with Signs of Heterogeneous Functional Anomalies.
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DOI：
10.4049/jimmunol.2300639
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发表时间：
2024-02-01
期刊：
影响因子：
--
通讯作者：
Sandberg JK
中科院分区：
文献类型：
--
作者：
Kammann T;Gorin JB;Parrot T;Gao Y;Ponzetta A;Emgård J;Maleki KT;Sekine T;Rivera-Ballesteros O;Karolinska COVID-19 Study Group;Gredmark-Russ S;Rooyackers O;Skagerberg M;Eriksson LI;Norrby-Teglund A;Mak JYW;Fairlie DP;Björkström NK;Klingström J;Ljunggren HG;Aleman S;Buggert M;Strålin K;Sandberg JK
严重COVID-19后的短暂数值MAIT细胞恢复最终失败。暂时恢复的MAIT细胞显示异质性功能损伤。MAIT细胞数量和功能下降与PD-1高水平相关。粘膜相关不变T（MAIT）细胞是人类中丰富的非常规T细胞群体，并且在针对微生物感染的免疫防御中发挥重要作用。严重的COVID-19与MAIT细胞的强烈激活和这些细胞从循环中的损失有关。在本研究中，我们研究了MAIT细胞在严重COVID-19后恢复的能力。在纵向配对分析中，MAIT细胞最初在出院后4个月在大多数患者中在数量和表型上反弹。然而，反弹的MAIT细胞显示出持续活化的迹象，CD 69，CD 38和HLA-DR的表达升高。尽管许多患者的MAIT细胞功能恢复，但一个亚组显示出主要是PD-1高功能受损的MAIT细胞池。该特征与响应IL-12 + L-18的IFN-γ和颗粒酶B的低表达和低水平的多功能性相关。出乎意料的是，尽管总体T细胞计数恢复，但在9个月随访时MAIT细胞池的正常化失败，MAIT细胞数量明显下降，PD-1水平进一步增加。总之，这些结果表明MAIT细胞的不一致恢复的初始瞬时期是不持续的并且最终失败。先前住院的COVID-19患者的持续MAIT细胞损伤可能会对抗菌免疫和炎症产生影响，并可能导致COVID-19后的健康问题。
Transient numerical MAIT cell recovery after severe COVID-19 eventually fails. Temporarily recovering MAIT cells display heterogeneous functional impairment. Decline in MAIT cell numbers and function associated with a PD-1high profile. Mucosal-associated invariant T (MAIT) cells are an abundant population of unconventional T cells in humans and play important roles in immune defense against microbial infections. Severe COVID-19 is associated with strong activation of MAIT cells and loss of these cells from circulation. In the present study, we investigated the capacity of MAIT cells to recover after severe COVID-19. In longitudinal paired analysis, MAIT cells initially rebounded numerically and phenotypically in most patients at 4 mo postrelease from the hospital. However, the rebounding MAIT cells displayed signs of persistent activation with elevated expression of CD69, CD38, and HLA-DR. Although MAIT cell function was restored in many patients, a subgroup displayed a predominantly PD-1high functionally impaired MAIT cell pool. This profile was associated with poor expression of IFN-γ and granzyme B in response to IL-12 + L-18 and low levels of polyfunctionality. Unexpectedly, although the overall T cell counts recovered, normalization of the MAIT cell pool failed at 9-mo follow-up, with a clear decline in MAIT cell numbers and a further increase in PD-1 levels. Together, these results indicate an initial transient period of inconsistent recovery of MAIT cells that is not sustained and eventually fails. Persisting MAIT cell impairment in previously hospitalized patients with COVID-19 may have consequences for antimicrobial immunity and inflammation and could potentially contribute to post-COVID-19 health problems.
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影响因子：
1.3
作者：
Long Y;Hinks TSC
通讯作者：
Hinks TSC
影响因子：
1.3
作者：
Han, Fei;Zheng, Yichao;Leeansyah, Edwin
通讯作者：
Leeansyah, Edwin
DOI：
10.1126/science.aax6624
发表时间：
2019-10-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Constantinides MG;Link VM;Tamoutounour S;Wong AC;Perez-Chaparro PJ;Han SJ;Chen YE;Li K;Farhat S;Weckel A;Krishnamurthy SR;Vujkovic-Cvijin I;Linehan JL;Bouladoux N;Merrill ED;Roy S;Cua DJ;Adams EJ;Bhandoola A;Scharschmidt TC;Aubé J;Fischbach MA;Belkaid Y
通讯作者：
Belkaid Y
影响因子：
9.8
作者：
Boulouis, Caroline;Sia, Wan Rong;Leeansyah, Edwin
通讯作者：
Leeansyah, Edwin
影响因子：
8
作者：
Bister, Jonna;Guterstam, Ylva Crona;Bjorkstrom, Niklas K.
通讯作者：
Bjorkstrom, Niklas K.