Identification of T cell subpopulations exhibiting a high-degree of TCR-independent, IL-15-induced activation in pateints with acute hepatitis A

Abstract

Abstract During acute hepatitis A, pre-existing memory CD8+ T cells specific to hepatitis A virus-unrelated antigens are activated by IL-15 in a T-cell receptor (TCR)-independent manner, which is termed bystander activation, and these T cells contribute to liver injury (Immunity 2018, 48:161). However, it has been remained to be elucidated if other types of T cells are also activated by IL-15 without TCR engagement during acute hepatitis A. Here, we performed CITE-seq analysis in combination with single-cell RNA sequencing (scRNA-seq) using peripheral blood mononuclear cells (PBMCs) from patients with acute hepatitis A at acute and convalescent phases and healthy controls. In the scRNA-seq analysis, we used a gene set that was previously known to be upregulated by IL-15 in the absence of TCR stimulation to identify T-cell clusters that undergo TCR-independent, IL-15-induced activation. Among CD8+ T and γδ T cells, subclusters expressing CD45RO, CD57, and KLRG1 exhibited the highest module score of TCR-independent, IL-15-induced activation. Among MAIT cells, subclusters expressing CD8 and CD226 showed the highest module score of TCR-independent, IL-15-induced activation. Notably, these subclusters with the highest module score were exclusively found at the acute stage compared to the convalescent phase. In summary, T cell subpopulations exhibiting a high-degree of TCR-independent, IL-15-induced activation express distinct cell surface protein markers in patients with acute hepatitis A.