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IL-17/IL-10 double-producing T cells: new link between infections,
immunosuppression and acute myeloid leukemia
#MMPMID26174551
Musuraca G
; De Matteis S
; Napolitano R
; Papayannidis C
; Guadagnuolo V
; Fabbri F
; Cangini D
; Ceccolini M
; Giannini MB
; Lucchesi A
; Ronconi S
; Mariotti P
; Savini P
; Tani M
; Fattori PP
; Guidoboni M
; Martinelli G
; Zoli W
; Amadori D
; Carloni S
J Transl Med
2015[Jul]; 13
(?): 229
PMID26174551
show ga
BACKGROUND: Acute myeloid leukemia (AML) is an incurable disease with fatal
infections or relapse being the main causes of death in most cases. In
particular, the severe infections occurring in these patients before or during
any treatment suggest an intrinsic alteration of the immune system. In this
respect, IL-17-producing T helper (Th17) besides playing a key role in regulating
inflammatory response, tumor growth and autoimmune diseases, have been shown to
protect against bacterial and fungal pathogens. However, the role of Th17 cells
in AML has not yet been clarified. METHODS: T cell frequencies were assessed by
flow cytometry in the peripheral blood of 30 newly diagnosed AML patients and 30
age-matched healthy volunteers. Cytokine production was determined before and
after culture of T cells with either Candida Albicans or AML blasts. Statistical
analyses were carried out using the paired and unpaired two-tailed Student's t
tests and confirmed with the non parametric Wilcoxon signed-rank test. RESULTS: A
strong increase of Th17 cells producing immunosuppressive IL-10 was observed in
AML patients compared with healthy donors. In addition, stimulation of
AML-derived T cells with a Candida albicans antigen induced significantly lower
IFN-? production than that observed in healthy donors; intriguingly, depletion of
patient Th17 cells restored IFN-? production after stimulation. To address the
role of AML blasts in inducing Th17 alterations, CD4+ cells from healthy donors
were co-cultured with CD33+ blasts: data obtained showed that AML blasts induce
in healthy donors levels of IL-10-producing Th17 cells similar to those observed
in patients. CONCLUSIONS: In AML patients altered Th17 cells actively cause an
immunosuppressive state that may promote infections and probably tumor escape.
Th17 cells could thus represent a new target to improve AML immunotherapy.
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