Characterization of SARS-CoV-2 and common cold coronavirus-specific T-cell responses in MIS-C and Kawasaki disease children

Li En Hsieh, Alba Grifoni, John Sidney, Chisato Shimizu, Hiroko Shike, Nanda Ramchandar, Elizabeth Moreno, Adriana H. Tremoulet, Jane C. Burns, Alessandra Franco

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Abstract

The immunopathogenesis of multisystem inflammatory syndrome (MIS-C) in children that may follow exposure to SARS-CoV-2 is incompletely understood. Here, we studied SARS-CoV-2-specific T cells in MIS-C, Kawasaki disease (KD), and SARS-CoV-2 convalescent controls using peptide pools derived from SARS-CoV-2 spike or nonspike proteins, and common cold coronaviruses (CCC). Coordinated CD4+ and CD8+ SARS-CoV-2-specific T cells were detected in five MIS-C subjects with cross-reactivity to CCC. CD4+ and CD8+ T-cell responses alone were documented in three and one subjects, respectively. T-cell specificities in MIS-C did not correlate with disease severity and were similar to SARS-CoV-2 convalescent controls. T-cell memory and cross-reactivity to CCC in MIS-C and SARS-CoV-2 convalescent controls were also similar. The chemokine receptor CCR6, but not CCR9, was highly expressed on SARS-CoV-2-specific CD4+ but not on CD8+ T cells. Only two of 10 KD subjects showed a T-cell response to CCC. Enumeration of myeloid APCs revealed low cell precursors in MIS-C subjects compared to KD. In summary, children with MIS-C mount a normal T-cell response to SARS-CoV-2 with no apparent relationship to antecedent CCC exposure. Low numbers of tolerogenic myeloid DCs may impair their anti-inflammatory response.

Original languageEnglish (US)
Pages (from-to)123-137
Number of pages15
JournalEuropean Journal of Immunology
Volume52
Issue number1
DOIs
StatePublished - Jan 2022

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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