Activation or exhaustion of CD8+ T cells in patients with COVID-19

In addition to CD4+ T cells and neutralizing antibodies, CD8+ T cells contribute to protective immune responses against SARS-CoV-2 in patients with coronavirus disease 2019 (COVID-19), an ongoing pandemic disease. In patients with COVID-19, CD8+ T cells exhibiting activated phenotypes are commonly observed, although the absolute number of CD8+ T cells is decreased. In addition, several studies have reported an upregulation of inhibitory immune checkpoint receptors, such as PD-1, and the expression of exhaustion-associated gene signatures in CD8+ T cells from patients with COVID-19.

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Fig: Key features of exhausted CD8+ T cells. Exhausted CD8+ T cells are characterized by a loss of effector functions, sustained expression of inhibitory receptors, altered transcriptional and epigenetic landscape, and metabolic reprogramming

However, whether CD8+ T cells are truly exhausted during COVID-19 has been a controversial issue. In the present review, we summarize the current understanding of CD8+ T-cell exhaustion and describe the available knowledge on the phenotypes and functions of CD8+ T cells in the context of activation and exhaustion. We also summarize recent reports regarding phenotypical and functional analyses of SARS-CoV-2-specific CD8+ T cells and discuss long-term SARS-CoV-2-specific CD8+ T-cell memory.

Rha, MS., Shin, EC. Activation or exhaustion of CD8+ T cells in patients with COVID-19. Cell Mol Immunol (2021). https://doi.org/10.1038/s41423-021-00750-4

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