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LIGHT expression by mucosal T cells may regulate IFN-gamma expression in the intestine.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2004 Jul 01; Vol. 173 (1), pp. 251-8. - Publication Year :
- 2004
-
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.
- Subjects :
- Adult
CD2 Antigens physiology
Flow Cytometry
Gene Expression Profiling
Gene Expression Regulation
Humans
Leukocyte Common Antigens analysis
Membrane Proteins genetics
Tumor Necrosis Factor Ligand Superfamily Member 14
Tumor Necrosis Factor-alpha genetics
Interferon-gamma biosynthesis
Intestines immunology
Membrane Proteins physiology
T-Lymphocytes physiology
Tumor Necrosis Factor-alpha physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 173
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 15210782
- Full Text :
- https://doi.org/10.4049/jimmunol.173.1.251