Linked Life Data

20600326

Source:http://linkedlifedata.com/resource/pubmed/id/20600326

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-8-23
pubmed:abstractText
Autoimmune adverse events are a concern in patients treated with blocking anti-CTLA-4-mAb for solid and hematological tumors. Patient and mouse data on the contribution of a quantitative or qualitative defect of regulatory T cells (T(reg)) in this autoimmune phenomenon are conflicting. We have previously shown that a treatment course with blocking anti-CTLA-4-mAb in murine allogeneic bone marrow chimeras induces an antileukemic response in close association with systemic autoimmunity. Here, we used this model to investigate the effect of CTLA-4-blocking therapy on the kinetics of T(reg) frequency and function. As previously published, CTLA-4-blocking treatment, initiated on day 20 after bone marrow transplantation, led to overt autoimmunity by day 35. CD4(+)Foxp3(+) T(reg) frequency was determined (flowcytometry) on day 21, 23, 25 and 35: treated chimeras showed an expansion of CD4(+)Foxp3(+) T(reg) frequencies on day 25 and 35, without a prior frequency decrease. The T(reg) expansion occurred selectively in the recipient-derived CD4+ T-cell compartment. In vitro, purified CD4(+)CD25(+)FR4(high) T(reg) from 'day 35' autoimmune and control chimeras showed equal suppressive effects towards self-antigen-specific autoimmune T cells. Purified CD4(+)CD25(high)FR4(high) T(reg) from 'day 35' treated chimeras showed increased IL-10 and IFN-gamma mRNA-expression (RT-PCR) relative to control chimeras. In this model of CTLA-4-blockade-induced autoimmunity after allogeneic bone marrow transplantation, anti-CTLA-4-mAb gives rise to a progressive expansion - without a prior transient reduction - of T(reg) cells. T(reg) of autoimmune animals do not show a defect in in vitro suppressive function but show an in vivo activated cytokine profile, suggesting that the expansion occurs as a compensatory phenomenon to control autoimmunity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1879-0542
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
6
pubmed:volume
133
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
49-53
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:20600326-Animals, pubmed-meshheading:20600326-Antibodies, Blocking, pubmed-meshheading:20600326-Antigens, CD, pubmed-meshheading:20600326-Antigens, CD4, pubmed-meshheading:20600326-Autoimmunity, pubmed-meshheading:20600326-Bone Marrow Transplantation, pubmed-meshheading:20600326-CTLA-4 Antigen, pubmed-meshheading:20600326-Cell Proliferation, pubmed-meshheading:20600326-Cells, Cultured, pubmed-meshheading:20600326-Forkhead Transcription Factors, pubmed-meshheading:20600326-Immunosuppression, pubmed-meshheading:20600326-Immunotherapy, pubmed-meshheading:20600326-Interferon-gamma, pubmed-meshheading:20600326-Interleukin-10, pubmed-meshheading:20600326-Interleukin-2 Receptor alpha Subunit, pubmed-meshheading:20600326-Lymphocyte Activation, pubmed-meshheading:20600326-Mice, pubmed-meshheading:20600326-Mice, Inbred C3H, pubmed-meshheading:20600326-Neoplasms, pubmed-meshheading:20600326-T-Lymphocytes, Regulatory, pubmed-meshheading:20600326-Transplantation Chimera
pubmed:year
2010
pubmed:articleTitle
Murine bone marrow chimeras developing autoimmunity after CTLA-4-blockade show an expansion of T regulatory cells with an activated cytokine profile.
pubmed:affiliation
Laboratory of Experimental Transplantation, University of Leuven, Belgium.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't