Tobias Kammann, Jean-Baptiste Gorin, Tiphaine Parrot, Yu Gao, Andrea Ponzetta, Johanna Emgård, Kimia T. Maleki, Takuya Sekine, Olga Rivera-Ballesteros, Sara Gredmark-Russ, Olav Rooyackers, Magdalena Skagerberg, Lars I. Eriksson, Anna Norrby-Teglund, Jeffrey Y.W. Mak, David P. Fairlie, Niklas K. Björkström, Jonas Klingström, Hans-Gustaf Ljunggren, Soo Aleman, Marcus Buggert, Kristoffer Strålin, Johan K. Sandberg
{"title":"Dynamic MAIT Cell Recovery after Severe COVID-19 Is Transient with Signs of Heterogeneous Functional Anomalies","authors":"Tobias Kammann, Jean-Baptiste Gorin, Tiphaine Parrot, Yu Gao, Andrea Ponzetta, Johanna Emgård, Kimia T. Maleki, Takuya Sekine, Olga Rivera-Ballesteros, Sara Gredmark-Russ, Olav Rooyackers, Magdalena Skagerberg, Lars I. Eriksson, Anna Norrby-Teglund, Jeffrey Y.W. Mak, David P. Fairlie, Niklas K. Björkström, Jonas Klingström, Hans-Gustaf Ljunggren, Soo Aleman, Marcus Buggert, Kristoffer Strålin, Johan K. Sandberg","doi":"10.4049/jimmunol.2300639","DOIUrl":null,"url":null,"abstract":"<jats:title>Abstract</jats:title> 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+IL-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.","PeriodicalId":22698,"journal":{"name":"The Journal of Immunology","volume":"31 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Immunology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.4049/jimmunol.2300639","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract 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+IL-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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