After exposure to an antigen, CD8 T cells reach a decision point about their fate: to become either short-lived effector cells (SLECs) or memory progenitor effector cells (MPECs). SLECs are specialized in providing an immediate effector function but have a shorter lifespan and lower proliferative capacity compared to MPECs. Upon encountering the cognate antigen during an infection, CD8 T cells rapidly expand and then contract to a level that is maintained for the memory phase after the peak of the response. Studies have shown that the contraction phase is mediated by TGFβ and selectively targets SLECs, while sparing MPECs. The aim of this study is to investigate how the CD8 T cell precursor stage determines TGFβ sensitivity. Our results demonstrate that MPECs and SLECs have differential responses to TGFβ, with SLECs being more sensitive to TGFβ than MPECs. This difference in sensitivity is associated with the levels of TGFβRI and RGS3, and the SLEC-related transcriptional activator T-bet binding to the TGFβRI promoter may provide a molecular basis for increased TGFβ sensitivity in SLECs.
Keywords: CD8; MPEC; RGS3; SLEC; Smad; T-bet; TGFβ; tolerance.