Competition for Active TGFβ Cytokine Allows for Selective Retention of Antigen-Specific Tissue- Resident Memory T Cells in the Epidermal Niche

Immunity. 2021 Jan 12;54(1):84-98.e5. doi: 10.1016/j.immuni.2020.10.022. Epub 2020 Nov 18.


Following antigen-driven expansion in lymph node, transforming growth factor-β (TGFβ) is required for differentiation of skin-recruited CD8+ T cell effectors into epidermal resident memory T (Trm) cells and their epidermal persistence. We found that the source of TGFβ -supporting Trm cells was autocrine. In addition, antigen-specific Trm cells that encountered cognate antigen in the skin, and bystander Trm cells that did not, both displayed long-term persistence in the epidermis under steady-state conditions. However, when the active-TGFβ was limited or when new T cell clones were recruited into the epidermis, antigen-specific Trm cells were more efficiently retained than bystander Trm cells. Genetically enforced TGFβR signaling allowed bystander Trm cells to persist in the epidermis as efficiently as antigen-specific Trm cells in both contexts. Thus, competition between T cells for active TGFβ represents an unappreciated selective pressure that promotes the accumulation and persistence of antigen-specific Trm cells in the epidermal niche.

Keywords: TGFβ; antigen; bystander Trm; competition; keratinocytes; niche; resident memory T cells; skin; α(v)β(6); α(v)β(8).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • Bystander Effect
  • CD8-Positive T-Lymphocytes / immunology*
  • Cellular Microenvironment
  • Clone Cells
  • Epidermis / immunology*
  • Immunologic Memory
  • Keratinocytes / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Organ Specificity
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Signal Transduction
  • T-Cell Antigen Receptor Specificity
  • T-Lymphocytes, Regulatory / immunology*
  • Transforming Growth Factor beta / metabolism*


  • Receptors, Antigen, T-Cell, alpha-beta
  • Transforming Growth Factor beta