Dataset Information

COVID-19-Induced ARDS Is Associated with Decreased Frequency of Activated Memory/Effector T Cells Expressing CD11a⁺.

ABSTRACT: Preventing the progression to acute respiratory distress syndrome (ARDS) in COVID-19 is an unsolved challenge. The involvement of T cell immunity in this exacerbation remains unclear. To identify predictive markers of COVID-19 progress and outcome, we analyzed peripheral blood of 10 COVID-19-associated ARDS patients and 35 mild/moderate COVID-19 patients, not requiring intensive care. Using multi-parametric flow cytometry, we compared quantitative, phenotypic, and functional characteristics of circulating bulk immune cells, as well as SARS-CoV-2 S-protein-reactive T cells between the two groups. ARDS patients demonstrated significantly higher S-protein-reactive CD4⁺ and CD8⁺ T cells compared to non-ARDS patients. Of interest, comparison of circulating bulk T cells in ARDS patients to non-ARDS patients demonstrated decreased frequencies of CD4⁺ and CD8⁺ T cell subsets, with activated memory/effector T cells expressing tissue migration molecule CD11a⁺⁺. Importantly, survival from ARDS (4/10) was accompanied by a recovery of the CD11a⁺⁺ T cell subsets in peripheral blood. Conclusively, data on S-protein-reactive polyfunctional T cells indicate the ability of ARDS patients to generate antiviral protection. Furthermore, decreased frequencies of activated memory/effector T cells expressing tissue migratory molecule CD11a⁺⁺ observed in circulation of ARDS patients might suggest their involvement in ARDS development and propose the CD11a-based immune signature as a possible prognostic marker.

SUBMITTER: Anft M

PROVIDER: S-EPMC7543694 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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COVID-19-Induced ARDS Is Associated with Decreased Frequency of Activated Memory/Effector T Cells Expressing CD11a<sup>+</sup>.

Anft Moritz M Paniskaki Krystallenia K Blazquez-Navarro Arturo A Doevelaar Adrian A Seibert Felix S FS Hölzer Bodo B Skrzypczyk Sarah S Kohut Eva E Kurek Julia J Zapka Jan J Wehler Patrizia P Kaliszczyk Sviatlana S Bajda Sharon S Thieme Constantin J CJ Roch Toralf T Konik Margarethe Justine MJ Berger Marc Moritz MM Brenner Thorsten T Kölsch Uwe U Meister Toni L TL Pfaender Stephanie S Steinmann Eike E Tempfer Clemens C Watzl Carsten C Dolff Sebastian S Dittmer Ulf U Abou-El-Enein Mohamed M Westhoff Timm H TH Witzke Oliver O Stervbo Ulrik U Babel Nina N

Molecular therapy : the journal of the American Society of Gene Therapy 20201008 12

Preventing the progression to acute respiratory distress syndrome (ARDS) in COVID-19 is an unsolved challenge. The involvement of T cell immunity in this exacerbation remains unclear. To identify predictive markers of COVID-19 progress and outcome, we analyzed peripheral blood of 10 COVID-19-associated ARDS patients and 35 mild/moderate COVID-19 patients, not requiring intensive care. Using multi-parametric flow cytometry, we compared quantitative, phenotypic, and functional characteristics of c ...[more]

PMID: 33186542

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Project description:Immunotherapies aimed at enhancing natural or endogenous antitumor T-cell immunity in patients affected by advanced malignancies are currently being implemented in the clinic with promising results. In order to optimize therapeutic protocols and monitor the effectiveness of such therapies, reliable biomarkers are needed. We used CD11a, an integrin that is upregulated on the surface of effector and memory CD8+ T cells, and PD-1, an immunoregulatory receptor expressed by activated T cells, as biomarkers to identify, quantify and monitor endogenous tumor-reactive cytotoxic T lymphocytes (CTLs) in two mouse tumor models and in the peripheral blood of 12 patients affected by Stage IV melanoma. High expression levels of CD11a and PD-1 were detected among CD8+ T cells residing within primary and metastatic murine tumor sites, as well as in spontaneous murine breast cancer tissues. In the peripheral blood of melanoma patients, tumor antigen-specific CD8+ T cells were associated with a population of CD11ahigh CD8+ T cells that co-expressed high levels of PD-1. Healthy donors exhibited a comparatively much lower frequency of such PD-1+CD11ahighCD8+ T cells. Phenotypic analyses demonstrated that CD11ahighCD8+ T cells are proliferating (Ki67+) and activated (CD62L-CD69+). Increased CD11ahighCD8+ T cells and delayed tumor growth were observed in PD-1 deficient mice, suggesting that the antitumor effector functions of CD8+ T cells is compromised by an elevated expression of PD-1. The CD11ahighCD8+ T-cell population expresses high levels of PD-1 and presumably constitutes the cellular target of PD-1 blockade therapy. The expression level of CD11a and PD-1 by CD8+ T cells may therefore represent a novel biomarker to identify and monitor endogenous tumor-reactive CTLs. This may not only provide an immunological readout for evaluating the efficacy of immunotherapy but also contribute to the selection of cancer patients who are likely to benefit from anti-PD-1 therapy.

Dataset Information

COVID-19-Induced ARDS Is Associated with Decreased Frequency of Activated Memory/Effector T Cells Expressing CD11a⁺.

Publications

COVID-19-Induced ARDS Is Associated with Decreased Frequency of Activated Memory/Effector T Cells Expressing CD11a<sup>+</sup>.

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Dataset Information

COVID-19-Induced ARDS Is Associated with Decreased Frequency of Activated Memory/Effector T Cells Expressing CD11a+.

Publications

COVID-19-Induced ARDS Is Associated with Decreased Frequency of Activated Memory/Effector T Cells Expressing CD11a<sup>+</sup>.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

COVID-19-Induced ARDS Is Associated with Decreased Frequency of Activated Memory/Effector T Cells Expressing CD11a⁺.