Linked Life Data

11238667

Source:http://linkedlifedata.com/resource/pubmed/id/11238667

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-3-12
pubmed:abstractText
Chronic inflammatory autoimmune diseases such as diabetes, experimental autoimmune encephalomyelitis, and collagen-induced arthritis (CIA) are associated with type 1 (Th1, Tc1) T cell-dependent responses against autoantigens. Immune deviation toward type 2 (Th2, Tc2) response has been proposed as a potential means of gene therapy or immunomodulation to treat autoimmune diseases based on evidence that type 2 cytokines can prevent or alleviate these conditions. In this report we assessed the effects of elevated type 2 responses on CIA using transgenic mice expressing an IL-2R beta/IL-4R alpha chimeric cytokine receptor transgene specifically in T cells. In response to IL-2 binding, this chimeric receptor transduces IL-4-specific signals and dramatically enhances type 2 responses. In contrast to published reports of Th2-mediated protection, CIA was exacerbated in IL-2R beta/IL-4R alpha chimeric receptor transgenic mice, with increased disease incidence, severity, and earlier disease onset. The aggravated disease in transgenic mice was associated with an increase in type 2 cytokines (IL-4, IL-5, IL-10) and an increase in collagen-specific IgG1 levels. However, IFN-gamma production is not affected significantly in the induction phase of the disease. There is also an extensive eosinophilic infiltration in the arthritic joints of the transgenic animal, suggesting a direct contribution of type 2 response to joint inflammation. Taken together, our findings provide novel evidence that enhancement of a polyclonal type 2 response in immunocompetent hosts may exacerbate an autoimmune disease such as CIA, rather than serving a protective role. This finding raises significant caution with regard to the potential use of therapeutic approaches based on immune deviation toward type 2 responses.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
166
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4163-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11238667-Amino Acid Sequence, pubmed-meshheading:11238667-Animals, pubmed-meshheading:11238667-Arthritis, Experimental, pubmed-meshheading:11238667-Autoantibodies, pubmed-meshheading:11238667-Cattle, pubmed-meshheading:11238667-Cell Movement, pubmed-meshheading:11238667-Collagen, pubmed-meshheading:11238667-Cytokines, pubmed-meshheading:11238667-Eosinophils, pubmed-meshheading:11238667-Epitopes, T-Lymphocyte, pubmed-meshheading:11238667-Hindlimb, pubmed-meshheading:11238667-Immunoglobulin G, pubmed-meshheading:11238667-Lymphocyte Activation, pubmed-meshheading:11238667-Mice, pubmed-meshheading:11238667-Mice, Inbred C57BL, pubmed-meshheading:11238667-Mice, Inbred DBA, pubmed-meshheading:11238667-Mice, Transgenic, pubmed-meshheading:11238667-Molecular Sequence Data, pubmed-meshheading:11238667-Receptors, Cytokine, pubmed-meshheading:11238667-Receptors, Interleukin-2, pubmed-meshheading:11238667-Receptors, Interleukin-4, pubmed-meshheading:11238667-Recombinant Fusion Proteins, pubmed-meshheading:11238667-Th2 Cells, pubmed-meshheading:11238667-Transgenes, pubmed-meshheading:11238667-Up-Regulation
pubmed:year
2001
pubmed:articleTitle
Redirection of T cell effector function in vivo and enhanced collagen-induced arthritis mediated by an IL-2R beta/IL-4R alpha chimeric cytokine receptor transgene.
pubmed:affiliation
Division of Rheumatology, Department of Medicine, Vanderbilt University Medical School, Nashville, TN 37232, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't