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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2020-10-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.02243-20 |
| _version_ | 1818990164117028864 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T19:50:01Z |
| format | Article |
| id | doaj.art-a28bf7f6b21545bc87d37ee6e40a01c0 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-20T19:50:01Z |
| publishDate | 2020-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-a28bf7f6b21545bc87d37ee6e40a01c02022-12-21T19:28:20ZengAmerican Society for MicrobiologymBio2150-75112020-10-0111510.1128/mBio.02243-20Impaired Cytotoxic CD8<sup>+</sup> T Cell Response in Elderly COVID-19 PatientsJaana Westmeier0Krystallenia Paniskaki1Zehra Karaköse2Tanja Werner3Kathrin Sutter4Sebastian Dolff5Marvin Overbeck6Andreas Limmer7Jia Liu8Xin Zheng9Thorsten Brenner10Marc M. Berger11Oliver Witzke12Mirko Trilling13Mengji Lu14Dongliang Yang15Nina Babel16Timm Westhoff17Ulf Dittmer18Gennadiy Zelinskyy19Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, GermanyInstitute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyInstitute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyInstitute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, GermanyDepartment of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen, GermanyDepartment of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen, GermanyDepartment of Infectious Diseases, Union Hospital of Tonji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Infectious Diseases, Union Hospital of Tonji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen, GermanyDepartment of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen, GermanyDepartment of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, GermanyInstitute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyInstitute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Infectious Diseases, Union Hospital of Tonji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCenter for Translational Medicine, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr–University Bochum, Herne, GermanyMedical Department I, Marien Hospital Herne, University Hospital of the Ruhr University of Bochum, Bochum, GermanyInstitute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyInstitute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyABSTRACT 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.https://journals.asm.org/doi/10.1128/mBio.02243-20COVID-19SARS-CoV-2cytotoxic T cellsCD8+CD4+PD-1 |
| spellingShingle | 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 mBio COVID-19 SARS-CoV-2 cytotoxic T cells CD8+ CD4+ PD-1 |
| title | 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_short | 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 |
| topic | COVID-19 SARS-CoV-2 cytotoxic T cells CD8+ CD4+ PD-1 |
| url | https://journals.asm.org/doi/10.1128/mBio.02243-20 |
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