Differential Localization of T-bet and Eomes in CD8 T Cell Memory Populations

Abstract

In mice, two T-box transcription factors, T-bet and Eomes, drive the differentiation of CD8 T-cell lineages; however, little is known regarding their role in human CD8 T-cell differentiation. Here, we characterized T-bet and Eomes expression and localization within human CD8 memory T-cell populations. We find T-bet and Eomes are broadly expressed in human memory CD8 T cells, with increasing levels of T-bet and Eomes strongly correlating with differentiation from central memory to effector memory and effector subpopulations. In resting T-cells, T-bet levels directly correlate to subcellular localization, with a higher propensity for nuclear expression of T-bet within T-bethi cells and predominately cytoplasmic expression in T-betlo cells. Additionally, Eomes is also localized to either the nucleus or cytoplasm. Upon T-cell receptor stimulation, the percentage of T-cells that express T-bet dramatically increases, while the percentage of cells expressing Eomes remains largely unchanged across all memory populations. Interestingly, T-bet, but not Eomes, relocalizes to the nucleus in the majority of cells across all populations within 24 hours post-stimulation. These data indicate that T-bet and Eomes are likely regulated at the level of subcellular localization, potentially via different mechanisms. Together, these findings suggest a novel model for CD8 T-cell differentiation in humans based on the localization of T-bet and Eomes.

Infection History Determines the Differentiation State of Human CD8 + T Cells

“…1e). Concordant with data from McLane et al (25), T-bet was expressed in ranges stretching from negative to low (lo), low to intermediate (int), and intermediate to high (hi), whereas Eomes was expressed either in a negative-to-low or inter- (Fig. 1b).…”

“…This raises the question of whether T-bet and Eomes expression can be used to distinguish human virus-specific CD8 ϩ T cells with distinct functional programs. We and others have recently shown that T-bet and Eomes expression varies in human CD8 ϩ T-cell subsets and virus-specific populations (6,(25)(26)(27)(28). Furthermore, their expression levels were also shown to distinctly correspond to the expression of IL-7R␣, granzymes, and various coinhibitory receptors expressed by exhausted CD8 ϩ T cells (26,27,29).…”

Focusing and sustaining the antitumor CTL effector killer response by agonist anti-CD137 mAb

“…Previous studies revealed a relation of eomesodermin and CD137 costimulation (24,25). Eomes is involved in both favoring the expression of effector molecules (26) and favoring differentiation to memory T lymphocytes (27,28).…”

Chronic Infection by Mucoid Pseudomonas aeruginosa Associated with Dysregulation in T-Cell Immunity to Outer Membrane Porin F

“…Tbet was first defined as a hallmark transcription factor for differentiation of Th1 cells, and since then has often been taken as a biomarker of Th1 immunity (49); in Tbet knockout mice the key phenotype relates to Th1 defects (50,51). However, alterations in Tbet transcription may encompass programmatic changes in other cell types: CD8 cells, natural killer cells, innate lymphoid cells, dendritic cells, and B cells (52)(53)(54)(55)(56). The lipid second messenger, S1P and its receptor, S1PR1, control lymphoid organ egress, trafficking, and T-cell subset determination (57).…”