Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

CD16+ monocytes control T cell subset development in immune thrombocytopenia

Abstract

Immune thrombocytopenia (ITP), results from decreased platelet production and accelerated platelet destruction. Impaired CD4+CD25+ T cell (Treg) compartment and skewed Th1 and possibly Th17 responses have been described in ITP patients. The trigger for aberrant T cell polarization remains unknown. Since monocytes have a critical role in development and polarization of T cell subsets, we explored the contribution of monocyte subsets in control of Treg and Th development in patients with ITP. Unlike circulating classical CD14(hi)CD16(-) subpopulation, the CD16+ monocyte subset was expanded in ITP patients with low platelet counts on thrombopoietic agents and positively correlated with T cell CD4+IFN-γ+ levels, but negatively with circulating CD4(+)CD25(hi)Foxp3(+) and IL-17+Th cells. Using a coculture model, we found that CD16+ ITP monocytes promoted the expansion of IFN-γ+CD4+ cells, and concomitantly inhibited the proliferation of Tregs and IL-17+ Th cells. Th-1 polarizing cytokine IL-12, secreted following direct contact of patient T cell and CD16+ monocytes, was responsible for the inhibitory effect on Treg and IL-17+CD4+ cell proliferation. Our findings are consistent with ITP CD16+ monocytes promoting Th1 development, which in turn negatively regulates IL-17 and Treg induction. This underscores the critical role of CD16+ monocytes in the generation of potentially pathogenic Th responses in ITP.