Low Activation of CD8+ T Cells in response to Viral Peptides in Mexican Patients with Severe Dengue

• Published in: Journal of immunology research 2022-03, Vol.2022, p.9967594-13
• Main Authors: Estrada-Jiménez, Tania, Flores-Mendoza, Lilian, Ávila-Jiménez, Laura, Vázquez-Rodríguez, Carlos Francisco, Sánchez-Burgos, Gilma Guadalupe, Vallejo-Ruiz, Verónica, Reyes-Leyva, Julio
• Format: Article
• Language: English
• Subjects: Blood & organ donations; CD19 antigen; CD25 antigen; CD4 antigen; CD40L protein; CD45 antigen; CD8 antigen; CD8-Positive T-Lymphocytes; Cell activation; Cloning; Cytokines; Cytotoxicity; Dengue; Dengue fever; Dengue hemorrhagic fever; Disease; Epidemics; Flow cytometry; GATA-3 protein; Helper cells; Humans; Immunology; Immunopathogenesis; Immunoregulation; Infections; Leukocytes, Mononuclear; Lymphocytes; Lymphocytes T; Patients; Peptides; Perforin; Peripheral blood mononuclear cells; Proteins; Severe Dengue; Transcription factors; Viruses
• ISSN: 2314-8861; 2314-7156
• DOI: 10.1155/2022/9967594

It is acknowledged that antiviral immune response contributes to dengue immunopathogenesis. To identify immunological markers that distinguish dengue fever (DF) and dengue hemorrhagic fever (DHF), 113 patients with confirmed dengue infection were analyzed at 6 or 7 days after fever onset. Peripheral blood mononuclear cells (PBMC) were isolated, lymphocyte subsets and activation biomarkers were identified by flow cytometry, and differentiation of T helper (Th) lymphocytes was achieved by the relative expression analysis of T-bet (Th1), GATA-3 (Th2), ROR-γ (Th17), and FOXP-3 (T regulatory) transcription factors quantified by real-time PCR. CD8+, CD40L+, and CD45+ cells show higher numbers in DF compared to DHF patients, whereas CD4+, CD19+, and CD25+ cells show higher numbers in DHF than DF patients. High expression of GATA-3 accompanied by low expression of T-bet indicates predominance of Th2 response. In addition, higher expression of FOXP-3 and reduced functional cytotoxic T cells (CD8+perforin+) were observed in DHF patients. In further experiments, PBMC were stimulated ex vivo with dengue virus E, NS3, NS4, and NS5 peptides, and proliferating T cell subsets were determined. Lower proliferative responses to NS3 and NS4 peptides and reduced CD8+ cytotoxic T cells were observed in DHF patients. Our results suggest that immune response to dengue is dysregulated with predominance of CD4+ T cells, low activation of Th1 cells, and downregulation of the antiviral cytotoxic activity during severe dengue, likely induced by regulatory T cells.