Vδ2+ and α/β T cells show divergent trajectories during human aging

Abstract

Chronological aging and a variety of stressors are driving forces towards immunosenescence. While much attention was paid to the main T cell component, α/β T cells, few studies concentrate on the impact of age on γ/δ T cells' characteristics. The latter are important players of adaptive immunity but also have features associated with innate immunity. Vδ2+ are the main component of γ/δ while Vδ1+ T cells expand upon Cytomegalovirus (CMV) infection and with age. The Vδ2+ T cells are not influenced by persistent infections but do contribute to immunosurveillance against bacterial pathogens. Here, we focus on Vδ2+ T cells and report that their composition and functionality is not altered in older adults. We have performed a side-by-side comparison of α/β and Vδ2 cells by using two robust markers of T cell replicative history and cell differentiation (CD28 and CD27), and cytokine secretion (IFN-γ and TNF-α). Significant differences in Vδ2 versus α/β homeostasis, as well as phenotypic and functional changes emerged. However, the data strongly suggest a sustained functionality of the Vδ2 population with age, independently of the challenge. This suggests differential trajectories towards immunosenescence in α/β and Vδ2+ T cells, most likely explained by their intrinsic functions.

Human Peripheral Blood Gamma Delta T Cells: Report on a Series of Healthy Caucasian Portuguese Adults and Comprehensive Review of the Literature

“…Contrarily to what happens (and we observed) in αβ Tc, we found no significant correlation between the fraction of CD28-γδ Tc and age. This is agreement with that reported by Tan et al, who found that the proportion of terminally differentiated CD28-CD27-α/β Tc was significantly higher in the elderly compared to the young, but the fraction of CD28-CD27-Vδ2 Tc did not differ significantly between these age groups [215].…”

Proportions of blood-borne Vδ1+ and Vδ2+ T-cells are associated with overall survival of melanoma patients treated with ipilimumab

“…Vδ2+ cells were reported to have immunoregulatory activity (40, 41). Moreover, these cells can produce large amounts of IFN-γ and/or TNF-α, reflecting their killing and immunomodulatory function in collaboration with other components of the immune system (42, 43). …”

Markers of T Cell Senescence in Humans

“…For the γδ T cells, our work in 2014 suggested that, similar to MAIT, γδ T cells are either not susceptible to cellular aging or they simply do not follow the same rules as αβ T cells [ 86 ]. With further studies in the last two years, the data now seem to converge to the fact that Vδ2 (a subset of the γδ) does not follow the same markers as CD4 and CD8 (at least for CD27, CD28) in terms of cytokine production [ 87 , 88 ]. Eberl et al also tested the biological relevance of ligating KLRG-1 on Vδ2 and it does not have the inhibitory effect as shown on CD4, CD8 and even natural killer (NK) cells [ 89 ].…”