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. 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.
【저자키워드】 COVID-19, SARS-CoV-2, aging, PD-1, Cytotoxic T cells, CD8+, perforin, granzyme, CD4+, 【초록키워드】 viruses, Vaccine development, coronavirus, T cells, SARS-COV-2 infection, Infection, immunopathology, virus, CD4, CD8, T cell, cells, severity of COVID-19, acute infection, phenotype, Mild, age, information, T cell response, COVID-19 patients, COVID-19 patient, Elderly patient, Cytotoxic T cell, Impaired Cellular Immunity, acute respiratory syndrome, younger patients, disease course, Express, infected cell, effector memory, killing, implication, Cell, produced, responsible, analyzed, characterized, contribute, absence, induce, terminally differentiated, 【제목키워드】 elderly, CD8, response, cytotoxic, Impaired,