The transcription factor T-bet is induced by IL-15 and thymic agonist selection and controls CD8αα(+) intraepithelial lymphocyte development

Immunity. 2014 Aug 21;41(2):230-43. doi: 10.1016/j.immuni.2014.06.018.


CD8αα(+) intraepithelial lymphocytes (IELs) are instrumental in maintaining the epithelial barrier in the intestine. Similar to natural killer cells and other innate lymphoid cells, CD8αα(+) IELs constitutively express the T-box transcription factor T-bet. However, the precise role of T-bet for the differentiation or function of IELs is unknown. Here we show that mice genetically deficient for T-bet lacked both TCRαβ(+) and TCRγδ(+) CD8αα(+) IELs and thus are more susceptible to chemically induced colitis. Although T-bet was induced in thymic IEL precursors (IELPs) as a result of agonist selection and interleukin-15 (IL-15) receptor signaling, it was dispensable for the generation of IELPs. Subsequently, T-bet was required for the IL-15-dependent activation, differentiation, and expansion of IELPs in the periphery. Our study reveals a function of T-bet as a central transcriptional regulator linking agonist selection and IL-15 signaling with the emergence of CD8αα(+) IELs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD8 Antigens / biosynthesis*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation / immunology
  • Colitis / chemically induced
  • Colitis / immunology
  • Epithelial Cells / immunology
  • Interleukin-15 / genetics*
  • Interleukin-15 / immunology
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology
  • Intestines / cytology
  • Intestines / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Receptors, Antigen, T-Cell, gamma-delta / genetics*
  • Receptors, Interleukin-15 / immunology
  • Signal Transduction / immunology
  • T-Box Domain Proteins / biosynthesis
  • T-Box Domain Proteins / genetics*


  • CD8 Antigens
  • CD8 antigen, alpha chain
  • Interleukin-15
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Interleukin-15
  • T-Box Domain Proteins
  • T-box transcription factor TBX21