T-box Transcription Factors Combine with the Cytokines TGF-β and IL-15 to Control Tissue-Resident Memory T Cell Fate

Immunity. 2015 Dec 15;43(6):1101-11. doi: 10.1016/j.immuni.2015.11.008.


Tissue-resident memory T (Trm) cells contribute to local immune protection in non-lymphoid tissues such as skin and mucosa, but little is known about their transcriptional regulation. Here we showed that CD8(+)CD103(+) Trm cells, independent of circulating memory T cells, were sufficient for protection against infection and described molecular elements that were crucial for their development in skin and lung. We demonstrated that the T-box transcription factors (TFs) Eomes and T-bet combined to control CD8(+)CD103(+) Trm cell formation, such that their coordinate downregulation was crucial for TGF-β cytokine signaling. TGF-β signaling, in turn, resulted in reciprocal T-box TF downregulation. However, whereas extinguishment of Eomes was necessary for CD8(+)CD103(+) Trm cell development, residual T-bet expression maintained cell surface interleukin-15 (IL-15) receptor β-chain (CD122) expression and thus IL-15 responsiveness. These findings indicate that the T-box TFs control the two cytokines, TGF-β and IL-15, which are pivotal for CD8(+)CD103(+) Trm cell development and survival.

Keywords: T-box transcription factors; TGF-β; Tissue-resident memory T cells; peripheral immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Down-Regulation
  • Flow Cytometry
  • Gene Expression Regulation / immunology
  • Immunologic Memory / immunology*
  • Interleukin-15 / immunology*
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Knockout
  • Polymerase Chain Reaction
  • T-Box Domain Proteins / immunology*
  • T-Lymphocyte Subsets / immunology
  • Transforming Growth Factor beta / immunology*


  • Eomes protein, mouse
  • Interleukin-15
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Transforming Growth Factor beta