Linked Life Data

11683572

Source:http://linkedlifedata.com/resource/pubmed/id/11683572

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-10-30
pubmed:abstractText
CTLA-4 is a T cell surface molecule that binds to the costimulatory molecules CD80 and CD86 on antigen-presenting cells and downregulates T cell function. Therefore, we wanted to test whether antigen-specific activated T cells could be inhibited through directed CTLA-4 signaling using a bispecific antibody (BiAb) capable of simultaneously binding to CTLA-4 and a tissue-specific antigen. The BiAb was prepared by linking two separate monoclonal antibodies against CTLA-4 and the thyroid-stimulating hormone receptor (TSHR). The mouse B cell lymphoma line M12 (H2(d)) was used to induce alloreactive T cells in CBA/J mice (H2(k)); M12 cells stably transfected with the cDNA encoding murine TSHR (mM12) were used to restimulate the alloresponse in vitro. Results of assays for in vitro T cell proliferation, IL-2 production, and cytotoxicity in the presence of BiAb demonstrated that the BiAb could inhibit the T cell alloresponse when stimulated with mM12 cells but not with M12 cells. This effect was dependent on binding of TSHR-bound BiAb to CTLA-4, since the addition of soluble CTLA-4-Ig blocked the inhibitory effect. Injection of mM12 cells, along with the BiAb, not with antibodies against TSHR or CTLA-4 either separately or together, into CBA/J mice (H2(k)) downregulated alloreactive T cell responses. Our study demonstrated that the presence of CTLA-4 signaling molecules on the surface of target cells can protect those cells from immune attack by antigen-specific T cells and suggested that a similar approach could have potential therapeutic value in transplant rejection and tissue-specific autoimmune diseases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1521-6616
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Academic Press.
pubmed:issnType
Print
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
136-45
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:11683572-Animals, pubmed-meshheading:11683572-Antibodies, Bispecific, pubmed-meshheading:11683572-Antibodies, Monoclonal, pubmed-meshheading:11683572-Antigens, CD, pubmed-meshheading:11683572-Antigens, Differentiation, pubmed-meshheading:11683572-Autoimmune Diseases, pubmed-meshheading:11683572-CTLA-4 Antigen, pubmed-meshheading:11683572-Cricetinae, pubmed-meshheading:11683572-Down-Regulation, pubmed-meshheading:11683572-Female, pubmed-meshheading:11683572-Immunoconjugates, pubmed-meshheading:11683572-Immunosuppressive Agents, pubmed-meshheading:11683572-Interleukin-2, pubmed-meshheading:11683572-Mice, pubmed-meshheading:11683572-Mice, Inbred BALB C, pubmed-meshheading:11683572-Mice, Inbred CBA, pubmed-meshheading:11683572-Organ Specificity, pubmed-meshheading:11683572-Receptors, Thyrotropin, pubmed-meshheading:11683572-T-Lymphocytes
pubmed:year
2001
pubmed:articleTitle
Targeted delivery of anti-CTLA-4 antibody downregulates T cell function in vitro and in vivo.
pubmed:affiliation
Department of Surgery, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't