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Changes of Host Immunity Mediated by IFN-γ+ CD8+ T Cells in Children with Adenovirus Pneumonia in Different Severity of Illness.

ABSTRACT: The host immunity of patients with adenovirus pneumonia in different severity of illness is unclear. This study compared the routine laboratory tests and the host immunity of human adenovirus (HAdV) patients with different severity of illness. A co-cultured cell model in vitro was established to verify the T cell response in vitro. Among 140 patients with confirmed HAdV of varying severity, the number of lymphocytes in the severe patients was significantly reduced to 1.91 × 109/L compared with the healthy control (3.92 × 109/L) and the mild patients (4.27 × 109/L). The levels of IL-6, IL-10, and IFN-γ in patients with adenovirus pneumonia were significantly elevated with the severity of the disease. Compared with the healthy control (20.82%) and the stable patients (33.96%), the percentage of CD8+ T cells that produced IFN-γ increased to 56.27% in the progressing patients. Adenovirus infection increased the percentage of CD8+ T and CD4+ T cells that produce IFN-γ in the co-culture system. The hyperfunction of IFN-γ+ CD8+ T cells might be related to the severity of adenovirus infection. The in vitro co-culture cell model could also provide a usable cellular model for subsequent experiments.

SUBMITTER: Zheng R

PROVIDER: S-EPMC8708941 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Changes of Host Immunity Mediated by IFN-γ+ CD8+ T Cells in Children with Adenovirus Pneumonia in Different Severity of Illness.

Zheng Ruilin R Li Yinghua Y Chen Danyang D Su Jingyao J Han Ning N Chen Haitian H Ning Zhihui Z Xiao Misi M Zhao Mingqi M Zhu Bing B

Viruses 20211128 12

The host immunity of patients with adenovirus pneumonia in different severity of illness is unclear. This study compared the routine laboratory tests and the host immunity of human adenovirus (HAdV) patients with different severity of illness. A co-cultured cell model in vitro was established to verify the T cell response in vitro. Among 140 patients with confirmed HAdV of varying severity, the number of lymphocytes in the severe patients was significantly reduced to 1.91 × 109/L comp ...[more]

PMID: 34960654

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Project description:IntroductionAlveolar epithelial regeneration depends on the activity of resident quiescent progenitor cells. Alveolar epithelial type II (AT2) cells are known as the alveolar epithelial progenitor cells. They exit quiescent state, proliferate rapidly in response to injury and differentiate into alveolar epithelial type I (AT1) cells to regenerate the damaged alveolar epithelium. Although AT2 cell plasticity has been a very intense field of research, the role of CD8 T cell response and their released cytokine IFN-γ, in regulating AT2 cell plasticity and alveolar epithelial repair and regeneration after injury remains largely unknown.MethodsWe used flow cytometry to quantify the amount of CD8 T cells in mouse lungs after bacterial pneumonia caused by Streptococcus pneumoniae. To determine whether CD8 T cells and their released cytokine IFN-γ are necessary for AT2 cell activity during alveolar epithelial regeneration, we performed loss of function studies using anti-CD8 or anti-IFN-γ monoclonal antibody (mAb) treatment in vivo. We assessed the effects of CD8 T cells and cytokine IFN-γ on AT2 cell differentiation capacity using the AT2- CD8 T cell co-culture system in vitro.ResultsWe detected a transient wave of accumulation of CD8 T cells in mouse lungs, which coincided with the burst of AT2 cell proliferation during alveolar epithelial repair and regeneration in mice following bacterial pneumonia caused by Streptococcus pneumoniae. Depletion of CD8 T cells or neutralization of cytokine IFN-γ using anti-CD8 or anti-IFN-γ monoclonal antibody significantly reduced AT2 cell proliferation and differentiation into AT1 cells in mice after bacterial pneumonia. Furthermore, co-culture of CD8 T cells or cytokine IFN-γ with AT2 cells promoted AT2-to-AT1 cell differentiation in both murine and human systems. Conversely, blockade of IFN-γ signaling abrogated the increase in AT2-to-AT1 cell differentiation in the AT2- CD8 T cell co-culture system.DiscussionOur data demonstrate that CD8 T-cell response and cytokine IFN-γ are necessary for promoting AT2 cell activity during alveolar epithelial repair and regeneration after acute lung injury caused by bacterial pneumonia.

Project description:Background Compared with children and immunocompromised patients, Adenovirus pneumonia in immunocompetent adults is less common. Evaluation of the applicability of severity score in predicting intensive care unit (ICU) admission of Adenovirus pneumonia is limited. Methods We retrospectively reviewed 50 Adenovirus pneumonia inpatients in Xiangtan Central Hospital from 2018 to 2020. Hospitalized patients with no pneumonia or immunosuppression were excluded. Clinical characteristics and chest image at the admission of all patients were collected. Severity scores, including Pneumonia severity index (PSI), CURB-65, SMART-COP, and PaO2/FiO2 combined lymphocyte were evaluated to compare the performance of ICU admission. Results Fifty inpatients with Adenovirus pneumonia were selected, 27 (54%) non-ICU and 23 (46%) ICU. Most patients were men (40 [80.00%]). Age median was 46.0 (IQR 31.0–56.0). Patients who required ICU care (n = 23) were more likely to report dyspnea (13[56.52%] vs 6[22.22%]; P = 0.002) and have lower transcutaneous oxygen saturation ([90% (IQR, 90–96), 95% (IQR, 93–96)]; P = 0.032). 76% (38/50) of patients had bilateral parenchymal abnormalities, including 91.30% (21/23) of ICU patients and 62.96% (17/27) of non-ICU patients. 23 Adenovirus pneumonia patients had bacterial infections, 17 had other viruses, and 5 had fungi. Coinfection with virus was more common in non-ICU patients than ICU patients (13[48.15%]VS 4[17.39%], P = 0.024), while bacteria and fungi not. SMART-COP exhibited the best ICU admission evaluation performance in Adenovirus pneumonia patients (AUC = 0.873, p < 0.001) and distributed similar in coinfections and no coinfections (p = 0.26). Conclusions In summary, Adenovirus pneumonia is not uncommon in immunocompetent adult patients who are susceptible to coinfection with other etiological illnesses. The initial SMART-COP score is still a reliable and valuable predictor of ICU admission in non-immunocompromised adult inpatients with adenovirus pneumonia.

Dataset Information

Changes of Host Immunity Mediated by IFN-γ+ CD8+ T Cells in Children with Adenovirus Pneumonia in Different Severity of Illness.

Publications

Changes of Host Immunity Mediated by IFN-γ<sup>+</sup> CD8<sup>+</sup> T Cells in Children with Adenovirus Pneumonia in Different Severity of Illness.

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