Human HKU1-reactive CD4 T cells are enriched for cytolytic potential that persists in older adults

J Infect Dis. 2025 Jan 15:jiaf026. doi: 10.1093/infdis/jiaf026. Online ahead of print.

Abstract

The emergence of SARS-CoV-2 increased interest in cellular immunity established by infections with human coronaviruses (HCoVs). Using PBMC from a cohort of human subjects collected prior to 2019, we assessed the abundance and phenotype of these CD4 T cells using cytokine Elispot assays. Unexpectedly, cytotoxic potential was uniquely enriched amongst HKU1-reactive CD4 T cells, as measured by quantification of granzyme producing cells. Also, although dramatic losses in HCoV-specific CD4 T cells 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.

Keywords: CD4 T cells; Coronavirus; Elispots; aging; cytotoxic cells; human; immunity.