Crossreactive CD4+ T cells to SARS-CoV-2, thought to originate from immune responses to common cold coronaviruses (CCCs), have been reported in up to 80% of SARS-CoV-2-naive individuals. This led to the hypothesis that encounters with CCCs may provide a degree of cross-protective immune memory. Now, a study in Immunity shows that SARS-CoV-2-crossreactive CD4+ T cells can be detected in almost all individuals tested and that these cells generally have a low functional avidity. At the same time, the authors identified highly expanded populations of low-avidity CD4+ T cells as a hallmark of severe COVID-19. This challenges the idea of a protective function of crossreactive CD4+ T cells and even raises the possibility that these cells may contribute to the risk of developing severe COVID-19. However, given the correlative nature of the study, causal links remain to be verified.
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Bacher, P. et al. Low-avidity CD4+ T cell responses to SARS-CoV-2 in unexposed individuals and humans with severe COVID-19. Immunity 53, 1258–1271 (2020)
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Flemming, A. Crossreactivity not so helpful after all?. Nat Rev Immunol 21, 70 (2021). https://doi.org/10.1038/s41577-020-00494-8
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DOI: https://doi.org/10.1038/s41577-020-00494-8