Co-Expression of TIGIT and Helios Marks Immunosenescent CD8 T Cells During Aging.

Aging leads to alterations in the immune system that result in ineffective responsiveness against pathogens. Features of this process, collectively known as immunosenescence, accumulate in CD8 T cells with age and have been ascribed to differentiation of these cells during the course of life. Here we aimed to identify novel markers in CD8 T cells associated with immunosenescence. Furthermore, we assessed how these markers relate to the aging-related accumulation of highly differentiated CD27CD28 cells. We found that co-expression of the transcription factor Helios and the aging-related marker TIGIT identifies CD8 T cells that fail to proliferate and show impaired induction of activation markers CD69 and CD25 in response to stimulation . Despite this, in blood of older adults we found TIGITHelios T cells to become highly activated during an influenza-A virus infection, but these higher frequencies of activated TIGITHelios T cells associate with longer duration of coughing. Moreover, in healthy individuals, we found that TIGITHelios CD8 T cells accumulate with age in the highly differentiated CD27CD28 population. Interestingly, TIGITHelios CD8 T cells also accumulate with age among the less differentiated CD27CD28 T cells before their transit into the highly differentiated CD27CD28 stage. This finding suggests that T cells with immunosenescent features become prominent at old age also within the earlier differentiation states of these cells. Our findings show that co-expression of TIGIT and Helios refines the definition of immunosenescent CD8 T cells and challenge the current dogma of late differentiation stage as proxy for T-cell immunosenescence.