Figure 1.

Innate T-cells in humans: current state of knowledge. (A, B) Innate T-cells are memory phenotype CD8 T-cells with innate functions. In humans, as their conventional memory counterparts (panel A, left), innate CD8 T-cells (panel A, middle) express TCRαβ and CD8, and have memory characteristics, as attested notably by Eomes expression and EMRA phenotype (CD45RA(+) CCR7(-)). They also share with NK cells some innate immune receptors such as KIR (KIR2D and KIR3DL1/2), NKG2A, CD122 and CD16. Co-expression of Eomes and KIR/NKG2A brings together the major fraction of CD8 T-cells able to free lytic granules in response to CD16 stimulation with antibodies (ADCC, antibody-dependent cellular cytotoxicity) and to produce IFN-γ upon innate-like stimulation by IL-12/IL-18 [(24) panel B]. As a result, CD8 T-cells co-expressing Eomes and KIR/NKG2A are identified as innate CD8 T-cells. A representative dot plot graph of Eomes(+) KIR/NKG2A(+) cells among CD8(+)CD3(+) PBMC from a healthy adult analyzed by flow cytometry is shown in panel A (right). (C) Ontogeny of innate CD8 T-cells. Innate CD8 T-cells have been evidenced in human cord blood, and like other fetal immune cells, they may be able to persist in adulthood. In mice, it is well-documented that they are produced in the thymus not only during the first stages of life but throughout a lifetime. With ageing, naive cells from the periphery differentiate into T-cell expressing innate features without antigen-stimulation. (D, E) Innate CD8 T-cells are part of the innateness gradient. PBMC from healthy donors were stained after 24h stimulation in vitro with IL-12/18 (D) or ex vivo (E), and analyzed by flow cytometry for innate-induced IFN-γ expression and mitochondrial mass (MTDR), respectively. Each point represents one healthy adult donor. A representative histogram is shown for each cell population. For detailed gating strategy, see Figure S1 .