GM-CSF-INDUCED GRANULOCYTIC MYELOID REGULATORY CELLS ARE ACTIVATED BY BACTERIAL LIPOPOLYSACCHARIDE TO SUPPRESS HUMAN T-CELL RESPONSES

Myeloid-derived suppressor cells (MDSC), initially found in malignant diseases, contributing to the development and / or course of cancer, autoimmune disorders, generalization of infections up to the development of sepsis, are functionally and phenotypically heterogeneous populations – monocytic and granulocytic MDSC. Granulocyte MDSC, or granulocytic regulatory cells (Gregs) induced by GMCSF, has been shown to inhibit the proliferative response of allogeneic lymphocytes in the presence of lipopolysaccharide (LPS) or fl agellin in various ways. Thus, in a situation where LPS, but not fl agellin, was present in cultures of allogeneic mixed lymphocytes, the introduction of Gregs induced by GMCSF significantly inhibited the proliferative responses of allogeneic lymphocytes. To the contrary, in the presence of fl agellin, Gregs rather increased the proliferation of responding responder cells, whereas in the absence of Gregs neither LPS nor fl agellin aff ected the proliferative response of responder cells. Determination of the gene expression profile in Gregs induced by GM-CSF or LPS revealed significantly (7–10-fold) increased transcription of genes encoding PTEN and ARGI (P <0.05), but not IL1B or TNF-alpha. It is assumed that microorganisms can use their own LPS in order to ensure PTEN-controlled energetic safety of immunosuppressive Gregs and enhance specific activity of the latter mediated by an ARGI product, the secreted arginase enzyme that limits the availability of arginine for the immune cells. Such a mechanism of immune escape allows the bacterial populations to survive better due to the weakening of antibacterial immunity.

myeloid-derived suppressor cells, granulocyte regulatory cells, lipopolysaccharide, fl agellin, mixed culture of allogeneic lymphocytes