Keratinocyte-Mediated Activation of the Cytokine TGF-β Maintains Skin Recirculating Memory CD8+ T Cells

Immunity. 2019 May 21;50(5):1249-1261.e5. doi: 10.1016/j.immuni.2019.03.002. Epub 2019 Apr 2.


Regulated activation of the cytokine TGF-β by integrins αvβ6 and αvβ8 expressed on keratinocytes is required for residence of epidermal-resident memory T cells, but whether skin-derived signals also affect recirculating memory cells in the skin remains unclear. Here, we show that after resolution of skin vaccinia virus (VV) infection, antigen-specific circulating memory CD8+ T cells migrated into skin. In mice lacking αvβ6 and αvβ8 integrins (Itgb6-/-Itgb8fl/fl-K14-cre), the absence of epidermal-activated TGF-β resulted in a gradual loss of E- or P-selectin-binding central and peripheral memory populations, which were rescued when skin entry was inhibited. Skin recirculating memory cells were required for optimal host defense against skin VV infection. These data demonstrate that skin migration can persist after resolution of local skin infection and that the cytokine environment within this nonlymphoid tissue shapes the differentiation state and persistence of the central and peripheral memory-T-cell pool.

Keywords: CD8(+) T cell memory; keratinocytes; skin; transforming growth factor beta; 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
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • CD8-Positive T-Lymphocytes / enzymology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Cytokines / immunology
  • Enzyme Activation
  • Female
  • Immunologic Memory / immunology*
  • Integrins / genetics
  • Integrins / metabolism*
  • Keratinocytes / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Skin / cytology
  • Skin / immunology
  • Transforming Growth Factor beta / metabolism*
  • Vaccinia virus / immunology*


  • Antigens, Neoplasm
  • Cytokines
  • Integrins
  • Transforming Growth Factor beta
  • integrin alphavbeta6
  • integrin alphavbeta8