Document Detail


IL-17-producing CD4(+) T cells, pro-inflammatory cytokines and apoptosis are increased in low risk myelodysplastic syndrome.
MedLine Citation:
PMID:  19210506     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Immunological responses are increasingly recognised as being important in the initiation and progression of myelodysplastic syndrome (MDS). Indeed, autoimmune diseases commonly occur in association with MDS, particularly in subtypes with a low risk of leukaemic transformation. This study showed for the first time that the numbers of CD3(+) CD4(+) IL-17 producing T cells (Th17) were markedly increased in low risk MDS compared with high risk MDS (P < 0.01). An inverse relationship between the numbers of Th17 cells and naturally occurring CD4(+)CD25(high) FoxP3(+) regulatory T cells (Tregs) were also described. The Th17:Tregs ratio was significantly higher in low risk disease (P < 0.005) compared with high risk MDS and was correlated with increased bone marrow (BM) apoptosis (P < 0.01). Tregs from MDS patients suppressed interferon-gamma (IFN-gamma) secretion by effector CD4(+) T cells but had no effect on interleukin (IL)-17 production. In addition, the serum levels of IL-7, IL-12, RANTES and IFN-gamma are significantly elevated in low risk MDS, while inhibitory factors, such as IL-10 and soluble IL-2 receptor, are significantly higher in high risk disease. The 'unfavourable' Th17:Tregs ratio in low risk MDS may explain the higher risk of autoimmunity and the improved response to immune suppression in patients with low risk MDS compared to those with high risk disease.
Authors:
Shahram Y Kordasti; Behdad Afzali; Ziyi Lim; Wendy Ingram; Janet Hayden; Linda Barber; Katie Matthews; Rajani Chelliah; Barbara Guinn; Giovanna Lombardi; Farzin Farzaneh; Ghulam J Mufti
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-02-03
Journal Detail:
Title:  British journal of haematology     Volume:  145     ISSN:  1365-2141     ISO Abbreviation:  Br. J. Haematol.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-18     Completed Date:  2009-06-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372544     Medline TA:  Br J Haematol     Country:  England    
Other Details:
Languages:  eng     Pagination:  64-72     Citation Subset:  IM    
Affiliation:
Department of Haematological Medicine, King's College London, The Rayne Institute, London, UK.
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MeSH Terms
Descriptor/Qualifier:
Aged
Apoptosis / physiology
Bone Marrow Cells / pathology
CD4-Positive T-Lymphocytes / immunology*
Case-Control Studies
Cell Separation / methods
Chemokine CCL5 / blood
Cytokines / blood*
Female
Flow Cytometry / methods
Humans
In Situ Nick-End Labeling
Interferon-gamma / blood
Interleukin-10 / blood
Interleukin-12 / blood
Interleukin-17 / immunology*
Interleukin-7 / blood
Male
Middle Aged
Myelodysplastic Syndromes / blood,  immunology*,  pathology
Receptors, Interleukin-2 / blood
Risk
Statistics, Nonparametric
Grant Support
ID/Acronym/Agency:
//Medical Research Council
Chemical
Reg. No./Substance:
0/Chemokine CCL5; 0/Cytokines; 0/Interleukin-17; 0/Interleukin-7; 0/Receptors, Interleukin-2; 130068-27-8/Interleukin-10; 187348-17-0/Interleukin-12; 82115-62-6/Interferon-gamma

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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