Genetic Influence on the Peripheral Differentiation Signature of Vδ2+ γδ and CD4+ αβ T Cells in Adults

Abstract

Adaptive as well as innate immune traits are variously affected by environmental and genetic influences, but little is known about the impact of genetics on the diversity, differentiation and functionality of γδ T cells in humans. Here, we analyzed a cohort of 95 middle-aged twins from the Danish Twin Registry. The differentiation status of peripheral αβ and γδ T cells was assessed by flow cytometry based on the surface expression of CD27, CD28 and CD45RA. Our data confirm the established associations of latent cytomegalovirus (CMV) infection with an accumulation of late differentiated memory T cells in the αβ compartment as well as in the Vδ1+ γδ T cell subset. A comparison of differentiation phenotypes of γδ and αβ T cells that were not affected by CMV seropositivity identified a significant correlation of early differentiated (ED) Vδ2+ and intermediate differentiated (ID) CD4+ T cells in monozygotic (MZ), but not in dizygotic (DZ) co-twins. Thus, our data suggest a genetic influence on the differentiation of γδ and αß T cell subsets.

Aging unconventionally: γδ T cells, iNKT cells, and MAIT cells in aging

“…This may be expected from the fact that Vδ1+ cells are more “adaptive-like” and their phenotype and function is influenced by stressors encountered during life, while Vδ2+ cells are more “innate-like” due to their semi-invariant TCR and exhibit a relatively stable distribution of differentiation phenotypes over time [70] , [86] , [87] . A recent twin study highlighted these differences, showing that Vδ1+ immune phenotype was influenced by the environment while Vδ2+ immune traits were more influenced by heritability [88] . Vδ2+ T cells also show hypo-methylated DNA and express genes associated with DNA damage repair, which may allow them to be more resistant to cellular senescence compared to Vδ2- T cells [89] .…”