tetano
Editor, Senior Moderator
Int J Mol Sci
. 2022 Dec 2;23(23):15201.
doi: 10.3390/ijms232315201.
Tolerogenic Dendritic Cells Induce Apoptosis-Independent T Cell Hyporesponsiveness of SARS-CoV-2-Specific T Cells in an Antigen-Specific Manner
Mats Van Delen[SUP] 1 [/SUP], Ibo Janssens[SUP] 1 [/SUP], Amber Dams[SUP] 1 [/SUP], Laurence Roosens[SUP] 2 [/SUP], Benson Ogunjimi[SUP] 3 4 5 6 [/SUP], Zwi N Berneman[SUP] 1 7 [/SUP], Judith Derdelinckx[SUP] 1 8 [/SUP], Nathalie Cools[SUP] 1 7 [/SUP]
Affiliations
Abstract
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[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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.
Keywords: T cell apoptosis; antigen specificity; severe COVID-19; tolerance; tolerogenic dendritic cells.
. 2022 Dec 2;23(23):15201.
doi: 10.3390/ijms232315201.
Tolerogenic Dendritic Cells Induce Apoptosis-Independent T Cell Hyporesponsiveness of SARS-CoV-2-Specific T Cells in an Antigen-Specific Manner
Mats Van Delen[SUP] 1 [/SUP], Ibo Janssens[SUP] 1 [/SUP], Amber Dams[SUP] 1 [/SUP], Laurence Roosens[SUP] 2 [/SUP], Benson Ogunjimi[SUP] 3 4 5 6 [/SUP], Zwi N Berneman[SUP] 1 7 [/SUP], Judith Derdelinckx[SUP] 1 8 [/SUP], Nathalie Cools[SUP] 1 7 [/SUP]
Affiliations
- PMID: 36499533
- DOI: 10.3390/ijms232315201
Abstract
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[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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.
Keywords: T cell apoptosis; antigen specificity; severe COVID-19; tolerance; tolerogenic dendritic cells.