Elevated CD4 + T Cell Senescence Associates with Impaired Immune Responsiveness in Severe COVID-19.

Autor: Zhang J; Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, China.; Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, China.; Biobank, Peking University Third Hospital, Beijing, China., Chang C; Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, China., Liang Z; Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, China., Hu T; Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, China., Yin Z; Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, China.; Biobank, Peking University Third Hospital, Beijing, China., Liang Y; Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, China., Zhang T; Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, China.; Biobank, Peking University Third Hospital, Beijing, China., Ding Y; Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, China., Li X; Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, China., Gai X; Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, China., Yang X; Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, China.; Biobank, Peking University Third Hospital, Beijing, China., Li X; Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, China., Dong X; Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, China.; Biobank, Peking University Third Hospital, Beijing, China., Ren J; Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, China., Rao Y; Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, China., Wang J; Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, China., Yang J; Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, China., Xue L; Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, China.; Biobank, Peking University Third Hospital, Beijing, China., Sun Y; Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, China.
Jazyk: angličtina
Zdroj: Aging and disease [Aging Dis] 2024 Feb 17. Date of Electronic Publication: 2024 Feb 17.
DOI: 10.14336/AD.2024.0214-2
Abstrakt: Aging is a critical risk factor for unfavorable clinical outcomes among COVID-19 patients and may impact vaccine efficacy. However, whether the senescence of T cells is associated with severe COVID-19 outcome in elderly individuals is unclear. Using flow cytometry, we analyzed the frequency of senescent T cells (Tsens) in peripheral blood from 100 hospitalized elderly COVID-19 patients and compared differences between those with mild/moderate and severe/critical illness. We also assessed correlations between the percentage of Tsens and the quantity and quality of spike-specific antibodies by ELISA, neutralizing antibody test kit, and ELISPOT assay respectively, the cytokine production profile of COVID-19 reactive T cells, and plasma soluble factors by cytometric bead array (CBA). Our study found a significantly elevated level of CD4 + Tsens in patients with severe/critical disease compared to those with mild/moderate illness. Patients with a higher level of CD4 + Tsens (>19.78%) showed a decreased survival rate compared to those with a lower level (≤19.78%). This is more pronounced among patients with breakthrough infections. The percentage of CD4 + Tsens was negatively correlated with spike-specific antibody titers, neutralization ability, and COVID-19 reactive IL-2 + CD4 + T cells. In addition, spike-specific antibody levels were positively correlated with IL-2 producing T cells and plasma IL-2 amount. Mechanistically, with defective CD40L, T cells from patients with CD4 + Tsens >19.78% were unable to support B cell proliferation and differentiation. Our data demonstrate that the percentage of CD4 + Tsens in peripheral blood may serve as a reliable biomarker for the prognosis of severe COVID-19 patients, especially in breakthrough infections. Therefore, restoring the immune response of CD4 + Tsens may be key to preventing severe illness and improving vaccine efficacy in older adults.
Databáze: MEDLINE
Externí odkaz: