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Title:
Decreased progenitor TCF1 + T-cells correlate with COVID-19 disease severity | Communications Biology
Description:
COVID-19, caused by SARS-CoV-2, can lead to a severe inflammatory disease characterized by significant lymphopenia. However, the underlying cause for the depletion of T-cells in COVID-19 patients remains incompletely understood. In this study, we assessed the presence of different T-cell subsets in the progression of COVID-19 from mild to severe disease, with a focus on TCF1 expressing progenitor T-cells that are needed to replenish peripheral T-cells during infection. Our results showed a preferential decline in TCF1+ progenitor CD4 and CD8+ T-cells with disease severity. This decline was seen in various TCF1+ subsets including naive, memory and effector-memory cells, and surprisingly, was accompanied by a loss in cell division as seen by a marked decline in Ki67 expression. In addition, TCF1+ T-cells showed a reduction in pro-survival regulator, BcL2, and the appearance of a new population of TCF1 negative caspase-3 expressing cells in peripheral blood from patients with severe disease. The decline in TCF1+ T-cells was also seen in a subgroup of severe patients with vitamin D deficiency. Lastly, we found that sera from severe patients inhibited TCF1 transcription ex vivo which was attenuated by a blocking antibody against the cytokine, interleukin-12 (IL12). Collectively, our findings underscore the potential significance of TCF1+ progenitor T-cells in accounting for the loss of immunity in severe COVID-19 and outline an array of markers that could be used to identify disease progression. This study shows that severity of disease in COVID-19 patients is characterized by the preferential loss of TCF1+ progenitor T-cells needed to self-renew and replenish the immune system.
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type:Organization
name:Centre de recherche de lâHôpital Maisonneuve-Rosemont
address:
name:Division of Immunology-Oncology, Centre de recherche de lâHôpital Maisonneuve-Rosemont, Montréal, Canada
type:PostalAddress
type:Organization
name:Nicholas Rozza
url:http://orcid.org/0000-0003-1713-8949
affiliation:
name:McGill University
address:
name:Division of Experimental Medicine, McGill University, Montreal, Canada
type:PostalAddress
type:Organization
name:Research Institute of the McGill University Health Center
address:
name:Department of Medicine, Research Institute of the McGill University Health Center, Montreal, Canada
type:PostalAddress
type:Organization
name:Richard Kremer
affiliation:
name:McGill University
address:
name:Division of Experimental Medicine, McGill University, Montreal, Canada
type:PostalAddress
type:Organization
name:Research Institute of the McGill University Health Center
address:
name:Department of Medicine, Research Institute of the McGill University Health Center, Montreal, Canada
type:PostalAddress
type:Organization
name:McGill University Health Centre
address:
name:Division of Medical Biochemistry, McGill University Health Centre, Montréal, Canada
type:PostalAddress
type:Organization
name:Catalin Mihalcioiu
affiliation:
name:McGill University Health Center
address:
name:Department of Medical Oncology, McGill University Health Center, Montreal, Canada
type:PostalAddress
type:Organization
name:Christopher E. Rudd
url:http://orcid.org/0000-0001-5295-9019
affiliation:
name:Universite de Montreal
address:
name:Départment of Medicine, Universite de Montreal, Montreal, Canada
type:PostalAddress
type:Organization
name:Université de Montréal
address:
name:Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, Canada
type:PostalAddress
type:Organization
name:Centre de recherche de lâHôpital Maisonneuve-Rosemont
address:
name:Division of Immunology-Oncology, Centre de recherche de lâHôpital Maisonneuve-Rosemont, Montréal, Canada
type:PostalAddress
type:Organization
name:McGill University
address:
name:Division of Experimental Medicine, McGill University, Montreal, Canada
type:PostalAddress
type:Organization
email:[email protected]
PostalAddress:
name:Départment of Medicine, Universite de Montreal, Montreal, Canada
name:Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, Canada
name:Division of Immunology-Oncology, Centre de recherche de lâHôpital Maisonneuve-Rosemont, Montréal, Canada
name:Division of Experimental Medicine, McGill University, Montreal, Canada
name:Department of Medicine, Research Institute of the McGill University Health Center, Montreal, Canada
name:Division of Medical Biochemistry, McGill University Health Centre, Montréal, Canada
name:Départment of Medicine, Universite de Montreal, Montreal, Canada
name:Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, Canada
name:Division of Immunology-Oncology, Centre de recherche de lâHôpital Maisonneuve-Rosemont, Montréal, Canada
name:Départment of Medicine, Universite de Montreal, Montreal, Canada
name:Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, Canada
name:Division of Immunology-Oncology, Centre de recherche de lâHôpital Maisonneuve-Rosemont, Montréal, Canada
name:Division of Experimental Medicine, McGill University, Montreal, Canada
name:Department of Medicine, Research Institute of the McGill University Health Center, Montreal, Canada
name:Division of Experimental Medicine, McGill University, Montreal, Canada
name:Department of Medicine, Research Institute of the McGill University Health Center, Montreal, Canada
name:Division of Medical Biochemistry, McGill University Health Centre, Montréal, Canada
name:Department of Medical Oncology, McGill University Health Center, Montreal, Canada
name:Départment of Medicine, Universite de Montreal, Montreal, Canada
name:Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, Canada
name:Division of Immunology-Oncology, Centre de recherche de lâHôpital Maisonneuve-Rosemont, Montréal, Canada
name:Division of Experimental Medicine, McGill University, Montreal, Canada
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