tetano
Editor, Senior Moderator
Commun Biol
. 2024 May 3;7(1):526.
doi: 10.1038/s42003-024-05922-2. Decreased progenitor TCF1 + T-cells correlate with COVID-19 disease severity
Thai Hien Tu[SUP] 1 2 3 [/SUP], Ami Grunbaum[SUP] 4 5 6 [/SUP], François Santinon[SUP] 1 2 3 [/SUP], Alexandra Kazanova[SUP] 1 2 3 [/SUP], Nicholas Rozza[SUP] 4 5 [/SUP], Richard Kremer[SUP] 4 5 6 [/SUP], Catalin Mihalcioiu[SUP] 7 [/SUP], Christopher E Rudd[SUP] 8 9 10 11 [/SUP]
Affiliations
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.
. 2024 May 3;7(1):526.
doi: 10.1038/s42003-024-05922-2. Decreased progenitor TCF1 + T-cells correlate with COVID-19 disease severity
Thai Hien Tu[SUP] 1 2 3 [/SUP], Ami Grunbaum[SUP] 4 5 6 [/SUP], François Santinon[SUP] 1 2 3 [/SUP], Alexandra Kazanova[SUP] 1 2 3 [/SUP], Nicholas Rozza[SUP] 4 5 [/SUP], Richard Kremer[SUP] 4 5 6 [/SUP], Catalin Mihalcioiu[SUP] 7 [/SUP], Christopher E Rudd[SUP] 8 9 10 11 [/SUP]
Affiliations
- PMID: 38702425
- PMCID: PMC11068881
- DOI: 10.1038/s42003-024-05922-2
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.