Direct Presentation of Antigen by Lymph Node Stromal Cells Protects Against CD8 T-Cell-Mediated Intestinal Autoimmunity

Fay C. Magnusson, Roland S. Liblau, Harald von Boehmer, Mikael J. Pittet, Je Wook Lee, Shannon J. Turley, Khashayarsha Khazaie

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


Background & Aims: Disruption of the enteric glial cell (EGC) network is an early pathologic feature in Crohn's disease. To determine the contribution of antigen-specific CD8 and CD4 T cells to the breakdown of the EGC network, we studied specific autoimmune targeting of an ectopic antigen expressed by EGCs. Methods: Transgenic mice (GFAP-HA), which express the influenza hemagglutinin (HA) in EGCs, were either crossed with mice transgenic for a T-cell receptor (TCR) specific for a major histocompatibility complex (MHC) class I epitope of HA (CL4-TCR) or were adoptively transferred with conventional CL4 T cells. These were compared with GFAP-HA mice transferred with conventional T cells specific for an MHC class II epitope of HA (6.5). Results: Both CD8 and CD4 T-cell subtypes were activated in vivo in an antigen-specific manner; however, they differed substantially in their ability to expand in the mesenteric lymph nodes, trigger proinflammatory cytokines, and induce autoimmune damage in the intestine. Direct presentation of antigen, provided by lymph node stromal cells, caused the activation and deletion of CD8 T cells. This mechanism of T-cell tolerance did not affect CD4 T cells, which produced antigen-specific lethal autoimmunity. Conclusions: Our observations support a recently identified mechanism of peripheral T-cell tolerance that specifically protects against autoimmunity mediated by conventional CD8 T cells. Furthermore, we show that conventional CD4 T cells are not affected by this mechanism of tolerance, and their targeting of EGCs produces lethal intestinal autoimmunity.

Original languageEnglish (US)
Pages (from-to)1028-1037
Number of pages10
Issue number4
StatePublished - Apr 2008

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


Dive into the research topics of 'Direct Presentation of Antigen by Lymph Node Stromal Cells Protects Against CD8 T-Cell-Mediated Intestinal Autoimmunity'. Together they form a unique fingerprint.

Cite this