Low responder T cell susceptibility to the suppressive function of regulatory T cells in patients with dilated cardiomyopathy

Objective The pathogenesis of dilated cardiomyopathy (DCM) is closely connected with dysfunction of the autoimmune system, and CD4(+)CD25(high)CD127(low/-)regulatory T (Treg) cells have a vital role in maintaining self-tolerance. In this study, we compared the frequency and regulatory function of Treg cells between DCM patients and normal controls. Methods and Results The frequencies of CD4(+)CD25(+) T cells in DCM patients were statistically decreased compared with normal controls (p<0.05) by flow cytometry, and the levels of FOXP3 mRNA and protein expression in PBMCs (peripheral blood mononuclear cells) of DCM patients were lower than those of normal controls (p<0.01), using real-time RT-PCR assay and western blot. Notably, the suppressive capacity of CD4(+)CD25(high)CD127(low/-) regulatory T cells of DCM patients acting on autologous CD4(+)CD25(-) responder T (Tresp) cells seemed to be partially impaired (43.83+/-3.19% suppression versus 63.17+/-3.66% in normal controls, p=0.01). Surprisingly, Treg cells from DCM patients efficiently suppressed the proliferation of Tresp cells from normal subjects to the similar level as Treg cells from normal subjects on autologous Tresp cells (p=0.286), whereas Treg cells of normal subjects poorly inhibited the proliferation of Tresp cells from DCM patients. Conclusion The defective capacity of Treg cells suppressing autologous Tresp cells is attributed to the increasing resistance of Tresp cells to inhibition of Treg cells in DCM patients. Therefore, strategies to improve the susceptibility of Tresp cells to Treg cell-mediated suppression might benefit DCM patients.