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

作者:McLane Laura M; Banerjee Pinaki P; Cosma Gabriela L; Makedonas George; Wherry E John; Orange Jordan S; Betts Michael R*
来源:The Journal of Immunology, 2013, 190(7): 3207-3215.
DOI:10.4049/jimmunol.1201556

摘要

In mice, two T-box transcription factors, T-box expressed in T cells (T-bet) and eomesodermin (Eomes), drive the differentiation of CD8 T cell lineages; however, little is known regarding their role in human CD8 T cell differentiation. In this study, we characterized T-bet and Eomes expression and localization within human CD8 memory T cell populations. We find that 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-bet(hi) cells and predominantly cytoplasmic expression in T-bet(lo) cells. In addition, Eomes is also localized to either the nucleus or the cytoplasm. Upon TCR stimulation, the percentage of T cells that express T-bet dramatically increases, whereas the percentage of cells expressing Eomes remains largely unchanged across all memory populations. Of interest, T-bet, but not Eomes, relocalizes to the nucleus in the majority of cells across all populations within 24 h 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 that is based on the localization of T-bet and Eomes. The Journal of Immunology, 2013, 190: 3207-3215.

  • 出版日期2013-4-1