title: IL-17-producing CD4(+) T cells, pro-inflammatory cytokines and apoptosis are increased in low risk myelodysplastic syndrome.
abstract: 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.affiliation: Department of Haematological Medicine, King's College London, The Rayne Institute, London, UK.
authors.forename: Shahram Y
authors.initials: SY
authors.lastname: Kordasti
authors.forename: Behdad
authors.initials: B
authors.lastname: Afzali
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Lim
authors.forename: Wendy
authors.initials: W
authors.lastname: Ingram
authors.forename: Janet
authors.initials: J
authors.lastname: Hayden
authors.forename: Linda
authors.initials: L
authors.lastname: Barber
authors.forename: Katie
authors.initials: K
authors.lastname: Matthews
authors.forename: Rajani
authors.initials: R
authors.lastname: Chelliah
authors.forename: Barbara
authors.initials: B
authors.lastname: Guinn
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lombardi
authors.forename: Farzin
authors.initials: F
authors.lastname: Farzaneh
authors.forename: Ghulam J
authors.initials: GJ
authors.lastname: Mufti
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000502:physiology; D001854:Bone Marrow Cells / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D002469:Cell Separation / Q000379:methods; D018946:Chemokine CCL5 / Q000097:blood; D016207:Cytokines / Q000097:blood*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D020381:Interleukin-17 / Q000276:immunology*; D015851:Interleukin-7 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000276:immunology* / Q000473:pathology; D015375:Receptors, Interleukin-2 / Q000097:blood; D012306:Risk; D018709:Statistics, Nonparametric
chemical_list: D018946:Chemokine CCL5; D016207:Cytokines; D020381:Interleukin-17; D015851:Interleukin-7; D015375:Receptors, Interleukin-2; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma