CD16 + monocytes control T-cell subset development in immune thrombocytopenia

摘要

Immune thrombocytopenia (ITP) results from decreased platelet production and accelerated platelet destruction. Impaired CD4 + regulatory 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. Because 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 classic CD14 hiCD16 - 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 hiFoxp3 + 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 after 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.