tetano
Editor, Senior Moderator
Front Immunol
. 2020 Nov 26;11:596553.
doi: 10.3389/fimmu.2020.596553. eCollection 2020.
Negative Clinical Evolution in COVID-19 Patients Is Frequently Accompanied With an Increased Proportion of Undifferentiated Th Cells and a Strong Underrepresentation of the Th1 Subset
Juan Francisco Guti?rrez-Bautista[SUP] 1 [/SUP], Antonio Rodriguez-Nicolas[SUP] 1 [/SUP], Antonio Rosales-Castillo[SUP] 2 [/SUP], Pilar Jim?nez[SUP] 1 [/SUP], Federico Garrido[SUP] 1 3 4 [/SUP], Per Anderson[SUP] 1 3 [/SUP], Francisco Ruiz-Cabello[SUP] 1 3 4 [/SUP], Miguel ?ngel L?pez-Ruz[SUP] 3 5 6 [/SUP]
Affiliations
Abstract
The severity of SARS-CoV-2 infection has been related to uncontrolled inflammatory innate responses and impaired adaptive immune responses mostly due to exhausted T lymphocytes and lymphopenia. In this work we have characterized the nature of the lymphopenia and demonstrate a set of factors that hinder the effective control of virus infection and the activation and arming of effector cytotoxic T CD8 cells and showing signatures defining a high-risk population. We performed immune profiling of the T helper (Th) CD4+ and T CD8+ cell compartments in peripheral blood of 144 COVID-19 patients using multiparametric flow cytometry analysis. On the one hand, there was a consistent lymphopenia with an overrepresentation of non-functional T cells, with an increased percentage of naive Th cells (CD45RA+, CXCR3-, CCR4-, CCR6-, CCR10-) and persistently low frequency of markers associated with Th1, Th17, and Th1/Th17 memory-effector T cells compared to healthy donors. On the other hand, the most profound alteration affected the Th1 subset, which may explain the poor T cells responses and the persistent blood virus load. Finally, the decrease in Th1 cells may also explain the low frequency of CD4+ and CD8+ T cells that express the HLA-DR and CD38 activation markers observed in numerous patients who showed minimal or no lymphocyte activation response. We also identified the percentage of HLA-DR+CD4+ T cells, PD-1+CD+4/CD8+ T cells in blood, and the neutrophil/lymphocyte ratio as useful factors for predicting critical illness and fatal outcome in patients with confirmed COVID-19.
Keywords: T cell response; T-CD8 lymphocytes flow cytometric immunophenotyping; Th lymphocytes; severe acute respiratory syndrome coronavirus 2; severe coronavirus disease 2019.
. 2020 Nov 26;11:596553.
doi: 10.3389/fimmu.2020.596553. eCollection 2020.
Negative Clinical Evolution in COVID-19 Patients Is Frequently Accompanied With an Increased Proportion of Undifferentiated Th Cells and a Strong Underrepresentation of the Th1 Subset
Juan Francisco Guti?rrez-Bautista[SUP] 1 [/SUP], Antonio Rodriguez-Nicolas[SUP] 1 [/SUP], Antonio Rosales-Castillo[SUP] 2 [/SUP], Pilar Jim?nez[SUP] 1 [/SUP], Federico Garrido[SUP] 1 3 4 [/SUP], Per Anderson[SUP] 1 3 [/SUP], Francisco Ruiz-Cabello[SUP] 1 3 4 [/SUP], Miguel ?ngel L?pez-Ruz[SUP] 3 5 6 [/SUP]
Affiliations
- PMID: 33324414
- PMCID: PMC7726249
- DOI: 10.3389/fimmu.2020.596553
Abstract
The severity of SARS-CoV-2 infection has been related to uncontrolled inflammatory innate responses and impaired adaptive immune responses mostly due to exhausted T lymphocytes and lymphopenia. In this work we have characterized the nature of the lymphopenia and demonstrate a set of factors that hinder the effective control of virus infection and the activation and arming of effector cytotoxic T CD8 cells and showing signatures defining a high-risk population. We performed immune profiling of the T helper (Th) CD4+ and T CD8+ cell compartments in peripheral blood of 144 COVID-19 patients using multiparametric flow cytometry analysis. On the one hand, there was a consistent lymphopenia with an overrepresentation of non-functional T cells, with an increased percentage of naive Th cells (CD45RA+, CXCR3-, CCR4-, CCR6-, CCR10-) and persistently low frequency of markers associated with Th1, Th17, and Th1/Th17 memory-effector T cells compared to healthy donors. On the other hand, the most profound alteration affected the Th1 subset, which may explain the poor T cells responses and the persistent blood virus load. Finally, the decrease in Th1 cells may also explain the low frequency of CD4+ and CD8+ T cells that express the HLA-DR and CD38 activation markers observed in numerous patients who showed minimal or no lymphocyte activation response. We also identified the percentage of HLA-DR+CD4+ T cells, PD-1+CD+4/CD8+ T cells in blood, and the neutrophil/lymphocyte ratio as useful factors for predicting critical illness and fatal outcome in patients with confirmed COVID-19.
Keywords: T cell response; T-CD8 lymphocytes flow cytometric immunophenotyping; Th lymphocytes; severe acute respiratory syndrome coronavirus 2; severe coronavirus disease 2019.