Effect of IL-7 and IL-15 on T cell phenotype in myelodysplastic syndromes.

Wen Dong,P.K Epling-Burnette,Lei Wu,Lili Yang,Tingting Ding,Xiubao Ren

doi:10.18632/oncotarget.8459

Wen Dong, P.K Epling-Burnette + Show 4 more

Open Access

https://doi.org/10.18632/oncotarget.8459

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Journal: Oncotarget	Publication Date: Mar 29, 2016
Citations: 3	License type: cc-by

Affiliation: Moffitt Cancer Center, Tianjin Medical University

Abstract

Aberrant T cell phenotype is one of the characteristics of myelodysplastic syndromes (MDS). In this study, we detected an increased concentration of IL-15 in the plasma of MDS patients (n = 20) compared with that in the plasma of healthy controls (n = 20). In MDS patients, reduced naïve CD4+ and CD8+ T cells [16.11 ± 6.56 vs. 24.11 ± 7.18 for CD4+ T cells (p < 0.001) and 13.15 ± 5.67 vs. 23.51 ± 6.25 for CD8+ T cells (p < 0.001)] were observed. The reduced naïve and increased effector memory T cells were significantly correlated with IL-15 plasma level. Then, the effect of IL-15 and IL-7 was tested in vitro. Peripheral blood mononuclear cells from MDS were treated for 15 days with IL-15. This treatment significantly decreased naïve CD4+ (p < 0.001) and CD8+ (p < 0.001) T cells and correspondingly increased terminal memory CD4+ and CD8+ T cells (p < 0.001). Treatment with IL-7 increased naïve CD4+ (p < 0.05) and CD8+ (p < 0.001) T cells. Our results indicated that exposure to high levels of IL-15 may be involved in the T cell phenotype conversion observed in MDS. IL-7 may be one of the promising therapeutic candidates for recovering the effector immune compartment in MDS patients.

Highlights

Myelodysplastic syndromes (MDS) include a spectrum of age-related hematological neoplasms characterized by dysplasia, cytopenias, and potential for acute myeloid leukemia (AML) progression [1]
myelodysplastic syndromes (MDS) patients were classified as refractory anemia with or without ringed sideroblast (n = 2, 10%), refractory cytopenia with multilineage dysplasia (n = 8, 40.0%), refractory anemia with excess blasts (RAEB)-1 (n = 3, 15%) and RAEB-2 (n = 4, 20%), and MDS-unclassified (n = 3, 20%) based on the classification criteria of the World Health Organization (WHO)
MDS is a clinically and molecularly heterogeneous group of clonal hematopoietic stem cell disorders that are singularly characterized by peripheral blood cytopenias from ineffective hematopoiesis and an increased but variable risk of leukemic transformation [19, 20]

Summary

Introduction

Myelodysplastic syndromes (MDS) include a spectrum of age-related hematological neoplasms characterized by dysplasia, cytopenias, and potential for acute myeloid leukemia (AML) progression [1]. Many studies have investigated the role of the immune system in MDS pathogenesis, such as T cell receptor V skewing [5], reduced CD4/ CD8 ratio, decreased natural killer (NK) cell function [6], contracted T cell repertoire, and loss of naïve T cells [7] These findings provide important insight into the disease pathogenesis. Aberrant cytokine expression is present in lymphoid and myeloid cells and is believed to contribute to the disease phenotype and outcome of patients [8, 9] Certain cytokines, such as TNF-α, IL-6, IL-8, and TGF-β, have been detected at increased concentrations in MDS; this finding indicates that these cytokines participate in the dysplastic features of the hematopoietic cells in the bone marrow [10, 11]

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