Linked Life Data

12675196

Source:http://linkedlifedata.com/resource/pubmed/id/12675196

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-4-4
pubmed:abstractText
Graft-versus-host-disease (GVHD) is a common and potentially fatal complication following bone marrow transplantation. This study was initiated to test whether MEB [n-butyrate 2-(4-morpholinyl) ethyl butyrate hydrochloride], a derivative of the G1 blocker butyric acid, could specifically inactivate the alloantigen-specific T cells that mediate GVHD. MEB was shown to inhibit proliferation in a one-way mixed lymphocyte reaction (MLR) in which spleen cells from C57BL/6 mice (H-2b) were stimulated with spleen cells from DBA/2 mice (H-2d). The addition of MEB to the MLR prevented the expansion of alloantigen-stimulated CD8+ and CD4+ T cells in association with decreased IL-2 production. In addition, MEB inhibited the CTL activity of CD8+ T cells from the MLR. Most importantly, T cells from the MEB-treated MLR, unlike T cells from an untreated MLR, were unable to induce the splenomegaly and increased serum TNF-alpha levels characteristic of acute GVHD when injected into B6D2F1 mice. The splenomegaly found in the B6D2F1 mice injected with T cells from an untreated MLR encompassed the expansion and activation of CD8+ T cells, CD4+ T cells, B cells and macrophages. In contrast, the spleens of mice injected with T cells from MEB-treated MLR looked essentially identical to those of control B6D2F1 mice in terms of the numbers and activation state of the spleen cell populations. Similarly, the increase in IFN-gamma and TNF-alpha production by CD4+ and CD8+ T cells from the spleens of mice undergoing acute GVHD was not observed if the mice were injected with T cells from an MEB-treated MLR instead of an untreated MLR. The use of MEB to inactivate host-specific T cells ex vivo underlines the potential clinical importance of this compound in the prevention and treatment of unwanted immune responses such as GVHD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0892-3973
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13-27
pubmed:dateRevised
2009-5-14
pubmed:meshHeading
pubmed-meshheading:12675196-Animals, pubmed-meshheading:12675196-Antigens, CD4, pubmed-meshheading:12675196-Antigens, CD8, pubmed-meshheading:12675196-Butyrates, pubmed-meshheading:12675196-Cell Transplantation, pubmed-meshheading:12675196-Cells, Cultured, pubmed-meshheading:12675196-Clonal Anergy, pubmed-meshheading:12675196-Cytokines, pubmed-meshheading:12675196-Disease Models, Animal, pubmed-meshheading:12675196-Graft vs Host Disease, pubmed-meshheading:12675196-Isoantigens, pubmed-meshheading:12675196-Lymphocyte Activation, pubmed-meshheading:12675196-Lymphocyte Culture Test, Mixed, pubmed-meshheading:12675196-Male, pubmed-meshheading:12675196-Mice, pubmed-meshheading:12675196-Mice, Inbred C57BL, pubmed-meshheading:12675196-Mice, Inbred DBA, pubmed-meshheading:12675196-Mice, Inbred Strains, pubmed-meshheading:12675196-Morpholines, pubmed-meshheading:12675196-Spleen, pubmed-meshheading:12675196-T-Lymphocytes, pubmed-meshheading:12675196-Tumor Necrosis Factor-alpha
pubmed:year
2003
pubmed:articleTitle
Butyric acid derivative induces allospecific T cell anergy and prevents graft-versus-host disease.
pubmed:affiliation
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA. gilbertkathleenm@uams.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't