Circulating T Cells Derived From Patients with Low Risk Myelodysplastic Syndromes Show Altered Chemokine Receptor Expression

The chemokine receptor expression by circulating T cells were investigated by multicolor flow cytometry for patients with newly diagnosed low risk MDS (N=16) and for healthy controls (N=18). CD3⁺CD8⁺ and CD3⁺CD8^- cells were examined for expression of CCR2-7, CXCR3-4 and CX3CR1 (only 7 unselected patients examined for CX3CR1 expression). CCR6 and CXCR4 expression was also investigated for specific T cell subsets defined by CD62L and CD45RA expression (naïve, central memory, effector memory and terminal effector). CX3CR1 expression was stratified for CD8⁺ and CD8^- subpopulations according to high, low and negative expression of CCR5.

Chemokine receptor profiles showed several differences between low risk MDS patients and controls. Total CD8⁺ T cells from MDS patients showed increased expression of CCR3 (p=0.005) and decreased expression of CCR7 and CCR4 (p=0.023 and p=0.036 respectively), whereas the CD8^- T cells from MDS patients showed increased expression of CX3CR1 (p=0.043). In contrast, CCR6 expression was increased only by CD8⁺ central memory T cells (p=0.044). Finally, CD8⁺CCR5^- and CD8^-CCR5^high cells from MDS patients showed increased expression of CX3CR1 compared with the controls (p=0.011 and p=0.049).

CCR7 is mainly expressed by central memory and naïve T cells whereas CX3CR1 is especially expressed by cytotoxic effector lymphocytes independent of the lymphocyte subclass (i.e. CD4, CD8, delta/gamma and NK cells). The observed changes are in line with a shift from naïve/central memory to effector/effector memory dominance, especially in the CD8⁺ population. A similar shift has been described previously using CD45RA and CD62L (Zou et al, Leukemia 2009). Our median values are in line with such a shift. CCR6 expression is associated with IL17 production both for CD8⁺ and CD4⁺cells, and increased levels of circulating CD4⁺ IL17 producing cells in low risk MDS have been described.

The chemokine receptor profiles of circulating T cells differ between low risk MDS patients and healthy controls, especially for the CD8⁺ T cell subset. These differences may be important for T cell trafficking and disease development, and they may reflect a shift from naïve to effector/effector memory cell dominance in low risk MDS.

No relevant conflicts of interest to declare.