TGF-β: A silent player regulating CD8 T cell memory

Clin Immunol. 2026 Jan:282:110612. doi: 10.1016/j.clim.2025.110612. Epub 2025 Oct 18.

Abstract

Transforming growth factor β (TGF-β) is recognized as an anti-inflammatory cytokine that negatively affects effector CD8 T cells. However, its impact is not confined to the effector CD8 T cell population; TGF-β also plays a role in suppressing naïve CD8 T cell activation, preserving stemness, and influencing the function and differentiation of memory CD8 T cells. Memory CD8 T cells are vital for eradicating pathogens that have previously infected the host. Both tissue-resident and central memory CD8 T cells have demonstrated a dependency on TGF-β for their differentiation. The mechanisms underlying many of these TGF-β effects remain unclear. This review summarizes the roles of TGF-β in various CD8 T cell subsets, with an emphasis on the memory T cell compartment, and discusses recent findings regarding its influence on memory CD8 T cell differentiation as well as open questions in the field.

Keywords: Dominant negative; Memory; Memory precursor effector; Short-lived effector; TGF-β signaling; Tissue-resident.

Publication types

  • Review

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes* / immunology
  • Cell Differentiation / immunology
  • Humans
  • Immunologic Memory* / immunology
  • Lymphocyte Activation / immunology
  • Memory T Cells* / immunology
  • Transforming Growth Factor beta* / immunology

Substances

  • Transforming Growth Factor beta