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. 2021 Jul 9;2:714239. doi: 10.3389/fragi.2021.714239

FIGURE 1.

FIGURE 1

Bystander activation of NKR expressing senescent T cells. 1) In the thymus, IL-14 release from thymocytes drives cell differentiation into innate CD8 single positive thymocytes which migrate to the periphery to generate into memory T cells. However, naïve CD8+ T cells have the capacity to differentiate to senescent T cells in an antigen-independent manner, through cytokine stimulation, also termed bystander activation. 2) NaIve T cells produce IFN-1 which drives IL-15 secretion in neighbouring immune cells and the subsequent establishment of senescent T cells. 3) Senescent T cells express NK receptors including NKG2A, NKG2C, and notably NKG2D with the adaptor molecule, DAP12, driven by SESTRIN. 4) IL-15 secretion drives the expansion of NKG2D and CD44+ expressing senescent cells. 5) SASP release by senescent T cells, i.e., IFN-α and TGF-α can drive generation of secondary bystander senescent T cells.