IL-17-producing CD4(+) T cells, pro-inflammatory cytokines and apoptosis are increased in low risk myelodysplastic syndrome.
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.
Kordasti
Shahram Y
SY
Department of Haematological Medicine, King's College London, The Rayne Institute, London, UK.
Afzali
Behdad
B
Lim
Ziyi
Z
Ingram
Wendy
W
Hayden
Janet
J
Barber
Linda
L
Matthews
Katie
K
Chelliah
Rajani
R
Guinn
Barbara
B
Lombardi
Giovanna
G
Farzaneh
Farzin
F
Mufti
Ghulam J
GJ
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
D018946:Chemokine CCL5; D016207:Cytokines; D020381:Interleukin-17; D015851:Interleukin-7; D015375:Receptors, Interleukin-2; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma