Suppression of T-Cell Proliferation by Normal Density Granulocytes Led to CD183 Downregulation and Cytokine Inhibition in T-Cells

Normal density granulocytes (NDGs) can suppress T-cell responses in a similar way as myeloid-derived suppressor cells (MDSCs). In this study, we tested the hypothesis that NDGs from healthy donors preferentially inhibit T helper 1 (Th1) cells and investigated the myeloid-derived suppressive effect in different T-cell populations. We found that NDG-induced suppression of T-cell proliferation was contact dependent, mediated by integrin CD11b, and dependent on NDG-production of reactive oxygen species (ROS). The suppression was rapid and occurred within the first few hours of coculture. The suppression did not influence the CD8(+)/CD4(+) ratio indicating an equal sensitivity in these populations. We further analyzed the CD4(+) T helper subsets and found that NDGs induced a loss of Th1 surface marker, CD183, that was unrelated to ligand-binding to CD183. In addition, we analyzed the Th1, Th2, and Th17 cytokine production and found that all cytokine groups were suppressed when T-cells were incubated with NDGs. We therefore concluded that NDGs do not preferentially suppress Th1-cells. Instead, NDGs generally suppress Th cells and cytotoxic T-cells but specifically downregulate the Th1 marker CD183.

Automated summary

This study found that normal density granulocytes (NDGs) do not preferentially suppress Th1 cells, but generally suppress Th cells and cytotoxic T-cells, while specifically downregulating the Th1 marker CD183.