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Generation of Cytotoxic T Cells and Dysfunctional CD8 T Cells in Severe COVID-19 Patients.
Gozzi-Silva, Sarah Cristina; Oliveira, Luana de Mendonça; Alberca, Ricardo Wesley; Pereira, Natalli Zanete; Yoshikawa, Fábio Seiti; Pietrobon, Anna Julia; Yendo, Tatiana Mina; de Souza Andrade, Milena Mary; Ramos, Yasmim Alefe Leuzzi; Brito, Cyro Alves; Oliveira, Emily Araujo; Beserra, Danielle Rosa; Orfali, Raquel Leão; Aoki, Valéria; Duarte, Alberto Jose da Silva; Sato, Maria Notomi.
  • Gozzi-Silva SC; Institute of Tropical Medicine, University of São Paulo, São Paulo 05403-000, Brazil.
  • Oliveira LM; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil.
  • Alberca RW; Institute of Tropical Medicine, University of São Paulo, São Paulo 05403-000, Brazil.
  • Pereira NZ; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil.
  • Yoshikawa FS; Institute of Tropical Medicine, University of São Paulo, São Paulo 05403-000, Brazil.
  • Pietrobon AJ; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil.
  • Yendo TM; Institute of Tropical Medicine, University of São Paulo, São Paulo 05403-000, Brazil.
  • de Souza Andrade MM; Laboratory of Dermatology and Immunodeficiencies 56 (LIM-56), Division of Dermatology, Medical School, University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar 470, São Paulo 05403-000, Brazil.
  • Ramos YAL; Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba 263-8522, Japan.
  • Brito CA; Institute of Tropical Medicine, University of São Paulo, São Paulo 05403-000, Brazil.
  • Oliveira EA; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil.
  • Beserra DR; Hospital das Clínicas of the University of São Paulo (HCFMUSP), University of São Paulo, São Paulo 05403-000, Brazil.
  • Orfali RL; Institute of Tropical Medicine, University of São Paulo, São Paulo 05403-000, Brazil.
  • Aoki V; Laboratory of Dermatology and Immunodeficiencies 56 (LIM-56), Division of Dermatology, Medical School, University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar 470, São Paulo 05403-000, Brazil.
  • Duarte AJDS; Institute of Tropical Medicine, University of São Paulo, São Paulo 05403-000, Brazil.
  • Sato MN; Laboratory of Dermatology and Immunodeficiencies 56 (LIM-56), Division of Dermatology, Medical School, University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar 470, São Paulo 05403-000, Brazil.
Cells ; 11(21)2022 Oct 25.
Article in English | MEDLINE | ID: covidwho-2090007
ABSTRACT
COVID-19, the infectious disease caused by SARS-CoV-2, has spread on a pandemic scale. The viral infection can evolve asymptomatically or can generate severe symptoms, influenced by the presence of comorbidities. Lymphopenia based on the severity of symptoms in patients affected with COVID-19 is frequent. However, the profiles of CD4+ and CD8+ T cells regarding cytotoxicity and antiviral factor expression have not yet been completely elucidated in acute SARS-CoV-2 infections. The purpose of this study was to evaluate the phenotypic and functional profile of T lymphocytes in patients with moderate and severe/critical COVID-19. During the pandemic period, we analyzed a cohort of 62 confirmed patients with SARS-CoV-2 (22 moderate cases and 40 severe/critical cases). Notwithstanding lymphopenia, we observed an increase in the expression of CD28, a co-stimulator molecule, and activation markers (CD38 and HLA-DR) in T lymphocytes as well as an increase in the frequency of CD4+ T cells, CD8+ T cells, and NK cells that express the immunological checkpoint protein PD-1 in patients with a severe/critical condition compared to healthy controls. Regarding the cytotoxic profile of peripheral blood mononuclear cells, an increase in the response of CD4+ T cells was already observed at the baseline level and scarcely changed upon PMA and Ionomycin stimulation. Meanwhile, CD8+ T lymphocytes decreased the cytotoxic response, evidencing a profile of exhaustion in patients with severe COVID-19. As observed by t-SNE, there were CD4+ T-cytotoxic and CD8+ T with low granzyme production, evidencing their dysfunction in severe/critical conditions. In addition, purified CD8+ T lymphocytes from patients with severe COVID-19 showed increased constitutive expression of differentially expressed genes associated with the caspase pathway, inflammasome, and antiviral factors, and, curiously, had reduced expression of TNF-α. The cytotoxic profile of CD4+ T cells may compensate for the dysfunction/exhaustion of TCD8+ in acute SARS-CoV-2 infection. These findings may provide an understanding of the interplay of cytotoxicity between CD4+ T cells and CD8+ T cells in the severity of acute COVID-19 infection.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Lymphopenia Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Limits: Humans Language: English Year: 2022 Document Type: Article Affiliation country: Cells11213359

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Lymphopenia Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Limits: Humans Language: English Year: 2022 Document Type: Article Affiliation country: Cells11213359