T Cell Recruitment to the Intestinal Stem Cell Compartment Drives Immune-Mediated Intestinal Damage after Allogeneic Transplantation

Immunity. 2019 Jul 16;51(1):90-103.e3. doi: 10.1016/j.immuni.2019.06.003. Epub 2019 Jul 2.


The key sites within the gastrointestinal (GI) tract where T cells mediate effector responses and the impact of these responses on intestinal stem cells (ISCs) remain unclear. Using experimental bone marrow transplantation to model immune-mediated GI damage and 3D imaging to analyze T cell localization, we found that the ISC compartment is the primary intestinal site targeted by T cells after transplantation. Recruitment to the crypt base region resulted in direct T cell engagement with the stem cell compartment and loss of crypt base columnar ISCs, which expressed both MHC classes I and II. Vasculature expressing the adhesion molecule MAdCAM-1 clustered near the crypt base, preferentially regulating crypt compartment invasion and ISC reduction without affecting T cell migration to villi. These findings indicate that allogeneic T cells rapidly access the stem cell niche after transplantation, and this targeted recruitment to the stem cell compartment results in ISC loss during immune-mediated GI damage.

Keywords: BMT; GVHD; ISCs; LPAM; MAdCAM-1; Paneth cells; allogeneic bone marrow transplantation; beta7 integrin; graft versus host disease; imaging of immunity; intestinal stem cells; mucosal immunology; transplantation.

Publication types

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

MeSH terms

  • Adult Stem Cells / immunology*
  • Animals
  • Blood Vessels / metabolism
  • Blood Vessels / pathology
  • Bone Marrow Transplantation*
  • Cell Adhesion Molecules / metabolism
  • Cell Movement
  • Cytotoxicity, Immunologic
  • Female
  • Humans
  • Imaging, Three-Dimensional
  • Intestinal Mucosa / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Middle Aged
  • Models, Animal
  • Mucoproteins
  • Stem Cell Niche / immunology*
  • T-Lymphocytes / immunology*
  • Transplantation, Homologous


  • Cell Adhesion Molecules
  • Madcam1 protein, mouse
  • Mucoproteins