Immunomodulatory effects of TGF-beta in the patients with immune thrombocytopenia

The novel concept of immune thrombocytopenia (ITP) pathogenesis is focused on CD4 + T cells, currently considered indispensable in stimulating B cells to produce anti-platelet antibodies.In this in vitro study, we have investigated CD4 + T cell profiles of ITP patients and immunomodulatory effects of TGF-β treatment.CD4 + T cells were isolated from peripheral blood mononuclear cells of healthy controls and ITP patients.After brief incubation, the levels of T helper signature cytokines and the number of T regulatory cells (Tregs) were determined.TGF-β immunomodulatory proprieties were analyzed by the alterations in cytokine production of IFNγ, IL-4, IL-10, IL-17, and IL-2 and Treg frequency, after six-day treatment.ITP patients had decreased level of IL-4 and IL-10, increased IL-17 level and augmented both IFNγ/IL-4 and IL-17/IL-10 ratio.Interestingly, in the six-day CD4 + T cell cultures without TGF-β, no statistically significant differences in cytokine levels between the control and ITP group were documented, except for IL-10 which was significantly lower.In ITP group treated with TGF-β, a significant increase of IL-10 as well as a decrease in IL-17/IL-10 ratio was detected, compared to TGF-β untreated ITP group.There was also an increase in the Treg frequency.The results of our study suggest that ITP patients have Th1 and Th17 biased cell-mediated immune response that can be corrected by enhanced TGF-β signaling.However, it appears that long-term culturing of the CD4 + T cells may not be a suitable experimental model for studying immunomodulating effects in ITP due to dynamic phenotype fluctuations of these cells in ex vivo conditions.