Shared acute phase traits in effector and memory human CD8 T cells

CD8 T cells have multiple functional properties that mediate acute phase and long-term immune protection. Several effector and memory CD8 T cell subsets have been described with diverse functionalities and marker profiles. In contrast to the many comprehensive mouse studies, most human studies lack samples from the acute infection phase, a major reason why current knowledge of human T cell subsets and differentiation remains incomplete, particularly with regard to the T cell heterogeneity early during the immune response. Here we analysed the human CD8 T cell response to yellow fever vaccination as the best-known model to study the human immune response to acute viral infection. We performed flow cytometry on 21 markers conventionally used in mice and in humans to describe differentiation, activation, cycling, and so-called effector functions. We found clearly distinct 'acute traits' at the peak of the response that are shared amongst all non-naïve antigen-specific subsets, including memory-differentiated cells. These acute traits were low BCL-2 and high KI67, CD38, HLA-DR, as well as increased Granzyme B and Perforin, previously attributed only to effector cells at the peak of the response. Furthermore, analysis of chromatin accessibility at the single cell level revealed that memory- and effector-differentiated cells clustered together specifically in the acute phase. Altogether, we demonstrate 'acute traits' across differentiation subsets, and point out the need to discriminate the differentiation states when studying human CD8 T cells that undergo an acute response.