Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2004-9-22
pubmed:abstractText
Intestinal autoimmune diseases are thought to be associated with a breakdown in tolerance, leading to mucosal lymphocyte activation perhaps as a result of encounter with bacterium-derived Ag. To study mucosal CD8(+) T cell activation, tolerance, and polarization of autoimmune reactivity to self-Ag, we developed a novel (Fabpl(4x at -132)-OVA) transgenic mouse model expressing a truncated form of OVA in intestinal epithelia of the terminal ileum and colon. We found that OVA-specific CD8(+) T cells were partially tolerant to intestinal epithelium-derived OVA, because oral infection with Listeria monocytogenes-encoding OVA did not elicit an endogenous OVA-specific MHC class I tetramer(+)CD8(+) T cell response and IFN-gamma-, IL-4-, and IL-5-secreting T cells were decreased in the Peyer's patches, mesenteric lymph nodes, and intestinal mucosa of transgenic mice. Adoptive transfer of OVA-specific CD8(+) (OT-I) T cells resulted in their preferential expansion in the Peyer's patches and mesenteric lymph nodes and subsequently in the epithelia and lamina propria but failed to cause mucosal inflammation. Thus, CFSE-labeled OT-I cells greatly proliferated in these tissues by 5 days posttransfer. Strikingly, OT-I cell-transferred Fabpl(4x at -132)-OVA transgenic mice underwent a transient weight loss and developed a CD8(+) T cell-mediated acute enterocolitis 5 days after oral L. monocytogenes-encoding OVA infection. These findings indicate that intestinal epithelium-derived "self-Ag" gains access to the mucosal immune system, leading to Ag-specific T cell activation and clonal deletion. However, when Ag is presented in the context of bacterial infection, the associated inflammatory signals drive Ag-specific CD8(+) T cells to mediate intestinal immunopathology.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
173
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4324-30
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:15383561-Acute Disease, pubmed-meshheading:15383561-Administration, Oral, pubmed-meshheading:15383561-Adoptive Transfer, pubmed-meshheading:15383561-Amino Acid Sequence, pubmed-meshheading:15383561-Animals, pubmed-meshheading:15383561-Autoantigens, pubmed-meshheading:15383561-CD8-Positive T-Lymphocytes, pubmed-meshheading:15383561-Carrier Proteins, pubmed-meshheading:15383561-Cell Differentiation, pubmed-meshheading:15383561-Cell Line, pubmed-meshheading:15383561-Cell Movement, pubmed-meshheading:15383561-Cells, Cultured, pubmed-meshheading:15383561-Enterocolitis, pubmed-meshheading:15383561-Epitopes, T-Lymphocyte, pubmed-meshheading:15383561-Fatty Acid-Binding Proteins, pubmed-meshheading:15383561-Humans, pubmed-meshheading:15383561-Immune Tolerance, pubmed-meshheading:15383561-Immunity, Mucosal, pubmed-meshheading:15383561-Intestinal Mucosa, pubmed-meshheading:15383561-Listeria monocytogenes, pubmed-meshheading:15383561-Listeriosis, pubmed-meshheading:15383561-Lymph Nodes, pubmed-meshheading:15383561-Lymphocyte Activation, pubmed-meshheading:15383561-Mesentery, pubmed-meshheading:15383561-Mice, pubmed-meshheading:15383561-Mice, Inbred C57BL, pubmed-meshheading:15383561-Mice, Transgenic, pubmed-meshheading:15383561-Molecular Sequence Data, pubmed-meshheading:15383561-Ovalbumin, pubmed-meshheading:15383561-Peyer's Patches
pubmed:year
2004
pubmed:articleTitle
Intestinal epithelial antigen induces mucosal CD8 T cell tolerance, activation, and inflammatory response.
pubmed:affiliation
Division of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't