A colitogenic memory CD4+ T cell population mediates gastrointestinal graft-versus-host disease

J Clin Invest. 2016 Sep 1;126(9):3541-55. doi: 10.1172/JCI80874. Epub 2016 Aug 8.


Damage to the gastrointestinal tract is a major cause of morbidity and mortality in graft-versus-host disease (GVHD) and is attributable to T cell-mediated inflammation. In this work, we identified a unique CD4+ T cell population that constitutively expresses the β2 integrin CD11c and displays a biased central memory phenotype and memory T cell transcriptional profile, innate-like properties, and increased expression of the gut-homing molecules α4β7 and CCR9. Using several complementary murine GVHD models, we determined that adoptive transfer and early accumulation of β2 integrin-expressing CD4+ T cells in the gastrointestinal tract initiated Th1-mediated proinflammatory cytokine production, augmented pathological damage in the colon, and increased mortality. The pathogenic effect of this CD4+ T cell population critically depended on coexpression of the IL-23 receptor, which was required for maximal inflammatory effects. Non-Foxp3-expressing CD4+ T cells produced IL-10, which regulated colonic inflammation and attenuated lethality in the absence of functional CD4+Foxp3+ T cells. Thus, the coordinate expression of CD11c and the IL-23 receptor defines an IL-10-regulated, colitogenic memory CD4+ T cell subset that is poised to initiate inflammation when there is loss of tolerance and breakdown of mucosal barriers.

Publication types

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

MeSH terms

  • Adoptive Transfer
  • Animals
  • Bone Marrow Cells / metabolism
  • CD11b Antigen / metabolism
  • CD11c Antigen / metabolism
  • CD18 Antigens / metabolism
  • CD4-Positive T-Lymphocytes / cytology*
  • Cell Proliferation
  • Cell Separation
  • Cytokines / metabolism
  • Disease Models, Animal
  • Flow Cytometry
  • Forkhead Transcription Factors / metabolism
  • Gastrointestinal Tract / immunology*
  • Graft vs Host Disease / immunology*
  • Humans
  • Immunoassay
  • Immunologic Memory*
  • Inflammation
  • Interleukin-10 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Phenotype
  • Receptors, Interleukin / metabolism


  • CD11b Antigen
  • CD11c Antigen
  • CD18 Antigens
  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • IL10 protein, mouse
  • Receptors, Interleukin
  • interleukin-23 receptor, mouse
  • Interleukin-10