CD16+ monocytes control T-cell subset development in immune thrombocytopenia.
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(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 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.
Laboratory of Complement Biology, New York Blood Center, NY, USA.
Hui
H
Zhong
Weili
W
Bao
Xiaojuan
X
Li
Allison
A
Miller
Caroline
C
Seery
Naznin
N
Haq
James
J
Bussel
Karina
K
Yazdanbakhsh
D016022:Case-Control Studies; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology* / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D017452:Receptors, IgG