Functional expression of 4-1BB (CD137) in the inflammatory tissue in Crohn's disease

Clin Immunol. 2004 Sep;112(3):239-46. doi: 10.1016/j.clim.2004.04.009.

Abstract

4-1BB ligand (L) expressed on antigen presenting cells (APC) interacts with 4-1BB, expressed on activated T cells and this interaction costimulates T cells to secrete cytokines and to proliferate. We investigated whether 4-1BB/4-1BBL interactions might be involved in the pathogenesis of Crohn's disease (CD). In immunohistochemistry, we found 4-1BB expression on lamina propria (LP) cells in inflamed and to a lesser extend in non-inflamed gut tissue from CD patients. mRNA levels for 4-1BB were also elevated in intestinal CD tissue. In contrast, only few 4-1BB-expressing cells were found in inflamed tissue from ulcerative colitis (UC) patients and almost no positive cells were found in control intestinal tissue. 4-1BB expression was better sustained on in vitro activated lamina propria T cells from CD patients compared to controls. Finally, agonistic anti-4-1BB antibody enhanced interferon-gamma (IFN-gamma) production and proliferation of lamina propria T cells from CD patients. Taken together, our data suggest that 4-1BB/4-1BBL interactions contribute to the persistence of gut inflammation in CD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-1BB Ligand
  • Adult
  • Aged
  • Antigens, CD
  • Cell Division
  • Crohn Disease / complications
  • Crohn Disease / genetics
  • Crohn Disease / metabolism*
  • Crohn Disease / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • Inflammation / complications
  • Inflammation / metabolism*
  • Inflammation / pathology*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / metabolism
  • Intestinal Mucosa / metabolism
  • Intestines / pathology
  • Kinetics
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Male
  • Middle Aged
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / metabolism*
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism*
  • T-Lymphocytes / metabolism
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • 4-1BB Ligand
  • Antigens, CD
  • RNA, Messenger
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • TNFRSF9 protein, human
  • TNFSF9 protein, human
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma