Impaired Cytotoxic CD8<sup>+</sup> T Cell Response in Elderly COVID-19 Patients

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces a T cell response that most likely contributes to virus control in COVID-19 patients but may also induce immunopathology. Until now, the cytotoxic T cell response has not been very well characterized in COVID-19...

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Autores principales:	Jaana Westmeier, Krystallenia Paniskaki, Zehra Karaköse, Tanja Werner, Kathrin Sutter, Sebastian Dolff, Marvin Overbeck, Andreas Limmer, Jia Liu, Xin Zheng, Thorsten Brenner, Marc M. Berger, Oliver Witzke, Mirko Trilling, Mengji Lu, Dongliang Yang, Nina Babel, Timm Westhoff, Ulf Dittmer, Gennadiy Zelinskyy
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	COVID-19 SARS-CoV-2 cytotoxic T cells CD8+ CD4+ PD-1 Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/a28bf7f6b21545bc87d37ee6e40a01c0
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spelling	oai:doaj.org-article:a28bf7f6b21545bc87d37ee6e40a01c02021-11-15T16:19:08ZImpaired Cytotoxic CD8<sup>+</sup> T Cell Response in Elderly COVID-19 Patients10.1128/mBio.02243-202150-7511https://doaj.org/article/a28bf7f6b21545bc87d37ee6e40a01c02020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02243-20https://doaj.org/toc/2150-7511ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces a T cell response that most likely contributes to virus control in COVID-19 patients but may also induce immunopathology. Until now, the cytotoxic T cell response has not been very well characterized in COVID-19 patients. Here, we analyzed the differentiation and cytotoxic profile of T cells in 30 cases of mild COVID-19 during acute infection. SARS-CoV-2 infection induced a cytotoxic response of CD8+ T cells, but not CD4+ T cells, characterized by the simultaneous production of granzyme A and B as well as perforin within different effector CD8+ T cell subsets. PD-1-expressing CD8+ T cells also produced cytotoxic molecules during acute infection, indicating that they were not functionally exhausted. However, in COVID-19 patients over the age of 80 years, the cytotoxic T cell potential was diminished, especially in effector memory and terminally differentiated effector CD8+ cells, showing that elderly patients have impaired cellular immunity against SARS-CoV-2. Our data provide valuable information about T cell responses in COVID-19 patients that may also have important implications for vaccine development. IMPORTANCE Cytotoxic T cells are responsible for the elimination of infected cells and are key players in the control of viruses. CD8+ T cells with an effector phenotype express cytotoxic molecules and are able to perform target cell killing. COVID-19 patients with a mild disease course were analyzed for the differentiation status and cytotoxic profile of CD8+ T cells. SARS-CoV-2 infection induced a vigorous cytotoxic CD8+ T cell response. However, this cytotoxic profile of T cells was not detected in COVID-19 patients over the age of 80 years. Thus, the absence of a cytotoxic response in elderly patients might be a possible reason for the more frequent severity of COVID-19 in this age group than in younger patients.Jaana WestmeierKrystallenia PaniskakiZehra KaraköseTanja WernerKathrin SutterSebastian DolffMarvin OverbeckAndreas LimmerJia LiuXin ZhengThorsten BrennerMarc M. BergerOliver WitzkeMirko TrillingMengji LuDongliang YangNina BabelTimm WesthoffUlf DittmerGennadiy ZelinskyyAmerican Society for MicrobiologyarticleCOVID-19SARS-CoV-2cytotoxic T cellsCD8+CD4+PD-1MicrobiologyQR1-502ENmBio, Vol 11, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	COVID-19 SARS-CoV-2 cytotoxic T cells CD8+ CD4+ PD-1 Microbiology QR1-502
spellingShingle	COVID-19 SARS-CoV-2 cytotoxic T cells CD8+ CD4+ PD-1 Microbiology QR1-502 Jaana Westmeier Krystallenia Paniskaki Zehra Karaköse Tanja Werner Kathrin Sutter Sebastian Dolff Marvin Overbeck Andreas Limmer Jia Liu Xin Zheng Thorsten Brenner Marc M. Berger Oliver Witzke Mirko Trilling Mengji Lu Dongliang Yang Nina Babel Timm Westhoff Ulf Dittmer Gennadiy Zelinskyy Impaired Cytotoxic CD8<sup>+</sup> T Cell Response in Elderly COVID-19 Patients
description	ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces a T cell response that most likely contributes to virus control in COVID-19 patients but may also induce immunopathology. Until now, the cytotoxic T cell response has not been very well characterized in COVID-19 patients. Here, we analyzed the differentiation and cytotoxic profile of T cells in 30 cases of mild COVID-19 during acute infection. SARS-CoV-2 infection induced a cytotoxic response of CD8+ T cells, but not CD4+ T cells, characterized by the simultaneous production of granzyme A and B as well as perforin within different effector CD8+ T cell subsets. PD-1-expressing CD8+ T cells also produced cytotoxic molecules during acute infection, indicating that they were not functionally exhausted. However, in COVID-19 patients over the age of 80 years, the cytotoxic T cell potential was diminished, especially in effector memory and terminally differentiated effector CD8+ cells, showing that elderly patients have impaired cellular immunity against SARS-CoV-2. Our data provide valuable information about T cell responses in COVID-19 patients that may also have important implications for vaccine development. IMPORTANCE Cytotoxic T cells are responsible for the elimination of infected cells and are key players in the control of viruses. CD8+ T cells with an effector phenotype express cytotoxic molecules and are able to perform target cell killing. COVID-19 patients with a mild disease course were analyzed for the differentiation status and cytotoxic profile of CD8+ T cells. SARS-CoV-2 infection induced a vigorous cytotoxic CD8+ T cell response. However, this cytotoxic profile of T cells was not detected in COVID-19 patients over the age of 80 years. Thus, the absence of a cytotoxic response in elderly patients might be a possible reason for the more frequent severity of COVID-19 in this age group than in younger patients.
format	article
author	Jaana Westmeier Krystallenia Paniskaki Zehra Karaköse Tanja Werner Kathrin Sutter Sebastian Dolff Marvin Overbeck Andreas Limmer Jia Liu Xin Zheng Thorsten Brenner Marc M. Berger Oliver Witzke Mirko Trilling Mengji Lu Dongliang Yang Nina Babel Timm Westhoff Ulf Dittmer Gennadiy Zelinskyy
author_facet	Jaana Westmeier Krystallenia Paniskaki Zehra Karaköse Tanja Werner Kathrin Sutter Sebastian Dolff Marvin Overbeck Andreas Limmer Jia Liu Xin Zheng Thorsten Brenner Marc M. Berger Oliver Witzke Mirko Trilling Mengji Lu Dongliang Yang Nina Babel Timm Westhoff Ulf Dittmer Gennadiy Zelinskyy
author_sort	Jaana Westmeier
title	Impaired Cytotoxic CD8<sup>+</sup> T Cell Response in Elderly COVID-19 Patients
title_short	Impaired Cytotoxic CD8<sup>+</sup> T Cell Response in Elderly COVID-19 Patients
title_full	Impaired Cytotoxic CD8<sup>+</sup> T Cell Response in Elderly COVID-19 Patients
title_fullStr	Impaired Cytotoxic CD8<sup>+</sup> T Cell Response in Elderly COVID-19 Patients
title_full_unstemmed	Impaired Cytotoxic CD8<sup>+</sup> T Cell Response in Elderly COVID-19 Patients
title_sort	impaired cytotoxic cd8<sup>+</sup> t cell response in elderly covid-19 patients
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/a28bf7f6b21545bc87d37ee6e40a01c0
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Impaired Cytotoxic CD8<sup>+</sup> T Cell Response in Elderly COVID-19 Patients

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