Decreased progenitor TCF1 + T-cells correlate with COVID-19 disease severity

• DOI: 10.1038/s42003-024-05922-2
• Publication Date: 2024-05-03T19:02:02Z
• Authors: Thai Hien Tu; Ami Grunbaum; François Santinon; Alexandra Kazanova; Nicholas Rozza; Richard Kremer; Catalin Mihalcioiu; Christopher E. Rudd
• Keywords: Male; Adult; CD4-Positive T-Lymphocytes; QH301-705.5; SARS-CoV-2; COVID-19; Middle Aged; CD8-Positive T-Lymphocytes; Severity of Illness Index; Article; T-Lymphocyte Subsets; Humans; Female; Hepatocyte Nuclear Factor 1-alpha; Biology (General); Aged

AbstractCOVID-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.