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  • 1
    Publication Date: 2012-10-19
    Description: 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- + 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- + 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.
    Keywords: Platelets and Thrombopoiesis
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 2
    Publication Date: 2012-10-19
    Description: B lymphocytes producing antiplatelet autoantibodies play a major role in autoimmune thrombocytopenia (ITP). However, certain B cells, including the human CD19 + CD24 hi CD38 hi subpopulation, possess regulatory functions mediated partly by IL-10. In a cohort of chronic ITP patients with low platelet counts who consisted of patients off treatment, we found a lower frequency of CD19 + CD24 hi CD38 hi in the peripheral compartment of nonsplenectomized patients ( P = .03). IL-10 expression after activation was decreased in all ITP circulating CD19 + subpopulations ( P 〈 .03), and inhibition of monocyte TNF-α expression by activated B cells was reduced in patients with platelet numbers of 〈 50 x 10 9 cells/L ( P = .001), indicating that regulatory B cells of patients with ITP are functionally impaired in their ability to dampen monocyte activation. Interestingly, in nonsplenectomized patients whose platelet counts were elevated after treatment with thrombopoietic agents, the frequency of CD19 + CD24 hi CD38 hi B cells was increased compared with those before treatment ( P = .02). Altogether, these data indicate a compromised regulatory B-cell com-partment as an additional defect in immune regulation in patients with chronic ITP that may be restored in responders to thrombopoietic treatment.
    Keywords: Platelets and Thrombopoiesis
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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