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. 2016 May 10;7(19):27479-88.
doi: 10.18632/oncotarget.8459.

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

Wen Dong  1 , Tingting Ding  2   3   4 , Lei Wu  2   3   4 , Xiubao Ren  2   3   4 , P K Epling-Burnette  5 , Lili Yang  2   3   4
Affiliations

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

Wen Dong et al. Oncotarget. .

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.

Keywords: IL-15; IL-7; T cells; myelodysplastic syndromes.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1. High levels of IL-15 and low levels of IL-7 in MDS patients compared with healthy donors
Measurement of a. IL-15 and b. IL-7 levels in plasma of MDS patients (n = 20) and healthy controls (n = 20). IL-15 and IL-7 were analyzed in duplicate using the Luminex Performance Human High Sensitivity Cytokine Magnetic Panel B (R&D). Wilcoxon rank sum test was used for analysis. p values for the case and control differences are shown at the top of each panel.
Figure 2
Figure 2. Naïve T cell subset defects in CD4+ and CD8+ T cells in MDS
Examples of naïve and memory flow dot plots are shown using peripheral blood from MDS patients. Naïve and memory subpopulations were defined with antibodies to CD45RA and CD62L a. Case and control differences between CD4+ b. and CD8+ c. T cell subpopulations were compared in 20 controls and 20 MDS patients using the Wilcoxon rank sum test. p values for the case and control differences are shown at the top of each panel.
Figure 3
Figure 3. Plasma IL-15 correlates with phenotypic abnormalities in MDS
Correlation between IL-15 plasma concentration and T cell subset percentages was conducted with correlation coefficients and p values for individual CD4 (top) and CD8 (bottom) panels. Highly significant correlations were observed between IL-15 and naïve cell population and effector T cells.
Figure 4
Figure 4. IL-7 restores the naïve T cell population in MDS
The effect of IL-7 and IL-15 on T cell phenotype was determined by culturing the cell in these cytokines in vitro. A typical flow panel of the effect of IL-7 and IL-15 on T cell subset distribution in healthy controls is presented a. The naïve and memory percentage of CD4+ b. and CD8+ c. T cells with or without IL-7 and IL-15 treatment of PBMCs of MDS patients (n = 20). PBMCs were stimulated with IL-7 (10 ng/mL) or IL-15 (10 ng/mL) for 15 days. PBMC in the absence of cytokine was used as control. Medium was changed and cytokine was re-added every three days. At day 15, cells were collected for phenotype evaluation based on their naïve and memory T cell subtype distribution using CD45RA and CD62L staining. Wilcoxon signed-rank test was used for analysis. p values for the differences are shown at the top of each panel.
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