NK-like CD8+ T cells in CMV-seronegative and -seropositive individuals

Abstract

Human cytomegalovirus (CMV) infection is widespread, with a seroprevalence exceeding 50% globally. Although typically asymptomatic in healthy individuals, CMV establishes latent infection, which significantly impacts the immune system, particularly influencing T and NK cell compartments. Notably, the frequency of CD8+ T cells expressing natural killer (NK) receptors, such as NKG2C and KIR, is increased in CMV-seropositive individuals compared to CMV-seronegative individuals. In the current study, we aimed to examine the characteristics of the NK-like CD8+ T cell population in the context of CMV infection. Single-cell RNA sequencing analysis identified common transcription factor IKZF2 (Helios) expression in NK-like CD8+ T cells. Among 7 IKZF2 clusters, 2 IKZF2 clusters (CD56 IKZF2 and CD161 IKZF2 clusters) were found to be increased in CMV-seropositive individuals. The CD56 IKZF2 cluster exhibited a unique TCR repertoire and characteristics similar to stem-like IKZF2 clusters, which are similar to the thymus CD8αα T-cell population. In contrast, the CD161 IKZF2 cluster exhibited a TCR repertoire similar to IKZF2 TEMRA clusters, which in turn are akin to that of IKZF2(-) TEMRA clusters. Taken together, our study has identified characteristics of the NK-like CD8+ T cell population in the context of CMV infection.