Tolerogenic Dendritic Cells Induce Apoptosis-Independent T Cell Hyporesponsiveness of SARS-CoV-2-Specific T Cells in an Antigen-Specific Manner

• Published in: International journal of molecular sciences Vol. 23; no. 23; p. 15201
• Main Authors: Van Delen, Mats, Janssens, Ibo, Dams, Amber, Roosens, Laurence, Ogunjimi, Benson, Berneman, Zwi N, Derdelinckx, Judith, Cools, Nathalie
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02.12.2022; MDPI
• Subjects: antigen specificity; Antigens; Apoptosis; CD4 antigen; CD8 antigen; Clonal deletion; Coronaviruses; COVID-19; Cytokines; Dendritic Cells; Disease; Genotype & phenotype; Humans; Immune Tolerance; Immunology; Inflammation; Interferon; Lymphocytes; Lymphocytes T; Monocytes; Peptides; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; severe COVID-19; Stimulation; T cell apoptosis; T-Lymphocytes; tolerance; tolerogenic dendritic cells; Tumor necrosis factor-TNF; Viral diseases; γ-Interferon; antigen specificity; tolerogenic dendritic cells; T cell apoptosis; tolerance; severe COVID-19
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232315201

Although the global pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still ongoing, there are currently no specific and highly efficient drugs for COVID-19 available, particularly in severe cases. Recent findings demonstrate that severe COVID-19 disease that requires hospitalization is associated with the hyperactivation of CD4 and CD8 T cell subsets. In this study, we aimed to counteract this high inflammatory state by inducing T-cell hyporesponsiveness in a SARS-CoV-2-specific manner using tolerogenic dendritic cells (tolDC). In vitro-activated SARS-CoV-2-specific T cells were isolated and stimulated with SARS-CoV-2 peptide-loaded monocyte-derived tolDC or with SARS-CoV-2 peptide-loaded conventional (conv) DC. We demonstrate a significant decrease in the number of interferon (IFN)-γ spot-forming cells when SARS-CoV-2-specific T cells were stimulated with tolDC as compared to stimulation with convDC. Importantly, this IFN-γ downmodulation in SARS-CoV-2-specific T cells was antigen-specific, since T cells retain their capacity to respond to an unrelated antigen and are not mediated by T cell deletion. Altogether, we have demonstrated that SARS-CoV-2 peptide-pulsed tolDC induces SARS-CoV-2-specific T cell hyporesponsiveness in an antigen-specific manner as compared to stimulation with SARS-CoV-2-specific convDC. These observations underline the clinical potential of tolDC to correct the immunological imbalance in the critically ill.