Characterization of T-Bet and Eomes in Peripheral Human Immune Cells

Abstract

The T-box transcription factors T-bet and Eomesodermin (Eomes) have been well defined as key drivers of immune cell development and cytolytic function. While the majority of studies have defined the roles of these factors in the context of murine T-cells, recent results have revealed that T-bet, and possibly Eomes, are expressed in other immune cell subsets. To date, the expression patterns of these factors in subsets of human peripheral blood mononuclear cells beyond T-cells remain relatively uncharacterized. In this study, we used multiparametric flow cytometry to characterize T-bet and Eomes expression in major human blood cell subsets, including total CD4+ and CD8+ T-cells, γδ T-cells, invariant NKT cells, natural killer cells, B-cells, and dendritic cells. Our studies identified novel cell subsets that express T-bet and Eomes and raise implications for their possible functions in the context of other human immune cell subsets besides their well-known roles in T-cells.

IL‐12 and IL‐15 induce the expression of CXCR6 and CD49a on peripheral natural killer cells

“…This transition may be supported by changes at a transcription factor level, for example IL‐15 and TGFβ have recently been shown to induce transition of Eomes low to Eomes high NK cells 29. However, CXCR6 was not upregulated under these conditions and T‐bet is already highly expressed on the majority of CD49a− peripheral blood NK cells, suggesting other mechanisms may be important 42.…”

Innate‐like CD8+ T‐cells and NK cells: converging functions and phenotypes

“…Thus, both CD56 dim NK cells and CD161+ CD8+ T‐cells are enriched for Eomes+T‐bet high cells,16, 107 while CD56 bright NK cells have an Eomes+T‐bet low phenotype,107 which is mirrored by CD8+ MAIT cells 108. Of note, CD161+ CD8+ T‐cells express higher levels of GrB and perforin even compared with their CD161− CD8+ T‐cell counterparts, although both populations contain similar frequencies of effector memory T‐cells and terminally differentiated CD8+ T‐cells 16…”

Biallelic mutations in IRF8 impair human NK cell maturation and function

“…The previously demonstrated gene dosage effect of E4BP4 suggests that repression but not absence of NFIL3, as seen in our patient, may lead to decreased mature NK cell numbers while not completely abrogating development (61), and placing NFIL3 downstream of IRF8 would be consistent with previous reports showing normal IRF8 expression in Nfil3 -/-mice (67). Similarly, Tbx21 -/-mice fail to generate mature NK cells and T-bet expression increases with NK cell maturation, with T-bet highly expressed in the CD56 dim NK cell subset (62,68). Both PRDM1 and HELIOS tune NK cell responsiveness; PRDM1 is a transcriptional repressor that binds directly to TNF and IFNG loci to regulate cytokine secretion in human NK cells (43) and is bound directly by IRF8 in B cells and macrophages (34), whereas HELIOS regulation is a mechanism of modulation of NK cell activity mediated through NKp46 ligation (69).…”