LIGHT expression by mucosal T cells may regulate IFN-gamma expression in the intestine.

Abstract

The TNF superfamily of cytokines play an important role in T cell activation and inflammation. Sustained expression of lymphotoxin-like inducible protein that competes with glycoprotein D for binding herpesvirus entry mediator on T cells (LIGHT) (TNFSF14) causes a pathological intestinal inflammation when constitutively expressed by mouse T cells. In this study, we characterized LIGHT expression on activated human T cell subsets in vitro and demonstrated a direct proinflammatory effect on regulation of IFN-gamma. LIGHT was induced in memory CD45RO CD4+ T cells and by IFN-gamma-producing CD4+ T cells. Kinetic analysis indicated rapid induction of LIGHT by human lamina propria T cells, reaching maximal levels by 2-6 h, whereas peripheral blood or lymph node-derived T cells required 24 h. Further analysis of intestinal specimens from a 41 patient cohort by flow cytometry indicated membrane LIGHT induction to higher peak levels in lamina propria T cells from the small bowel or rectum but not colon, when compared with lymph node or peripheral blood. Independent stimulation of the LIGHT receptor, herpesvirus entry mediator, induced IFN-gamma production in lamina propria T cells, while blocking LIGHT inhibited CD2-dependent induction of IFN-gamma synthesis, indicating a role for LIGHT in the regulation of IFN-gamma and as a putative mediator of proinflammatory T-T interactions in the intestinal mucosa. Taken together, these findings suggest LIGHT-herpesvirus entry mediator mediated signaling as an important immune regulatory mechanism in mucosal inflammatory responses.

• Authors: Offer Cohavy, Jaclyn Zhou, Steve W Granger, Carl F Ware, Stephan R Targan
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 173 Issue 1 Pg. 251-8 (Jul 01 2004) ISSN: 0022-1767 [Print] United States
• PMID: 15210782 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CD2 Antigens
• Membrane Proteins
• TNFSF14 protein, human
• Tnfsf14 protein, mouse
• Tumor Necrosis Factor Ligand Superfamily Member 14
• Tumor Necrosis Factor-alpha
• Interferon-gamma
• Leukocyte Common Antigens

Topics

• Adult
• CD2 Antigens (physiology)
• Flow Cytometry
• Gene Expression Profiling
• Gene Expression Regulation
• Humans
• Interferon-gamma (biosynthesis)
• Intestines (immunology)
• Leukocyte Common Antigens (analysis)
• Membrane Proteins (genetics, physiology)
• T-Lymphocytes (physiology)
• Tumor Necrosis Factor Ligand Superfamily Member 14
• Tumor Necrosis Factor-alpha (genetics, physiology)