tetano
Editor, Senior Moderator
mBio
. 2020 Sep 18;11(5):e02243-20.
doi: 10.1128/mBio.02243-20.
Impaired Cytotoxic CD8 [SUP]+[/SUP] T Cell Response in Elderly COVID-19 Patients
Jaana Westmeier[SUP] 1 [/SUP], Krystallenia Paniskaki[SUP] 2 [/SUP], Zehra Karak?se[SUP] 1 [/SUP], Tanja Werner[SUP] 1 [/SUP], Kathrin Sutter[SUP] 1 3 [/SUP], Sebastian Dolff[SUP] 4 [/SUP], Marvin Overbeck[SUP] 5 [/SUP], Andreas Limmer[SUP] 5 [/SUP], Jia Liu[SUP] 6 3 [/SUP], Xin Zheng[SUP] 6 3 [/SUP], Thorsten Brenner[SUP] 5 [/SUP], Marc M Berger[SUP] 5 [/SUP], Oliver Witzke[SUP] 4 [/SUP], Mirko Trilling[SUP] 1 3 [/SUP], Mengji Lu[SUP] 1 3 [/SUP], Dongliang Yang[SUP] 6 3 [/SUP], Nina Babel[SUP] 2 7 8 [/SUP], Timm Westhoff[SUP] 9 [/SUP], Ulf Dittmer[SUP] 10 3 [/SUP], Gennadiy Zelinskyy[SUP] 10 3 [/SUP]
Affiliations
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[SUP]+[/SUP] T cells, but not CD4[SUP]+[/SUP] T cells, characterized by the simultaneous production of granzyme A and B as well as perforin within different effector CD8[SUP]+[/SUP] T cell subsets. PD-1-expressing CD8[SUP]+[/SUP] 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[SUP]+[/SUP] 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[SUP]+[/SUP] 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[SUP]+[/SUP] T cells. SARS-CoV-2 infection induced a vigorous cytotoxic CD8[SUP]+[/SUP] 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.
Keywords: CD4+; CD8+; COVID-19; PD-1; SARS-CoV-2; aging; cytotoxic T cells; granzyme; perforin.
. 2020 Sep 18;11(5):e02243-20.
doi: 10.1128/mBio.02243-20.
Impaired Cytotoxic CD8 [SUP]+[/SUP] T Cell Response in Elderly COVID-19 Patients
Jaana Westmeier[SUP] 1 [/SUP], Krystallenia Paniskaki[SUP] 2 [/SUP], Zehra Karak?se[SUP] 1 [/SUP], Tanja Werner[SUP] 1 [/SUP], Kathrin Sutter[SUP] 1 3 [/SUP], Sebastian Dolff[SUP] 4 [/SUP], Marvin Overbeck[SUP] 5 [/SUP], Andreas Limmer[SUP] 5 [/SUP], Jia Liu[SUP] 6 3 [/SUP], Xin Zheng[SUP] 6 3 [/SUP], Thorsten Brenner[SUP] 5 [/SUP], Marc M Berger[SUP] 5 [/SUP], Oliver Witzke[SUP] 4 [/SUP], Mirko Trilling[SUP] 1 3 [/SUP], Mengji Lu[SUP] 1 3 [/SUP], Dongliang Yang[SUP] 6 3 [/SUP], Nina Babel[SUP] 2 7 8 [/SUP], Timm Westhoff[SUP] 9 [/SUP], Ulf Dittmer[SUP] 10 3 [/SUP], Gennadiy Zelinskyy[SUP] 10 3 [/SUP]
Affiliations
- PMID: 32948688
- DOI: 10.1128/mBio.02243-20
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[SUP]+[/SUP] T cells, but not CD4[SUP]+[/SUP] T cells, characterized by the simultaneous production of granzyme A and B as well as perforin within different effector CD8[SUP]+[/SUP] T cell subsets. PD-1-expressing CD8[SUP]+[/SUP] 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[SUP]+[/SUP] 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[SUP]+[/SUP] 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[SUP]+[/SUP] T cells. SARS-CoV-2 infection induced a vigorous cytotoxic CD8[SUP]+[/SUP] 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.
Keywords: CD4+; CD8+; COVID-19; PD-1; SARS-CoV-2; aging; cytotoxic T cells; granzyme; perforin.