Human HKU1-Reactive CD4 T Cells Are Enriched for Cytolytic Potential That Persists in Older Adults

The emergence of severe acute respiratory syndrome coronavirus 2 increased interest in cellular immunity established by infections with human coronaviruses (HCoVs). Using peripheral blood mononuclear cells from a cohort of human subjects collected prior to 2019, we assessed the abundance and phenotype of these CD4 T cells using cytokine enzyme-linked immunosorbent spot assays. Unexpectedly, cytotoxic potential was uniquely enriched among HKU1-reactive CD4 T cells, as measured by quantification of granzyme-producing cells. Also, although dramatic losses in HCoV-specific CD4 T-cell abundance for OC43-, NL63-, and 229E-specific cells were observed in older subjects relative to younger adults, HKU1-reactive cells exhibited minimal age-dependent differences in this phenotype.