CD4+/CD25+ T-Lymphocytes and Th1/Th2 regulation in dilated cardiomyopathy.

OBJECTIVE Autoimmune mechanisms are often involved in the pathogenesis of Dilated Cardiomyopathy (DCM) and Th1 immune response against cardiac antigens plays a pivotal role in disease development. METHODS IL-2 receptor (CD4+/CD25+) and cytokines IL-2, IFN-γ, IL-10 were studied in 42 patients (17 with DCM - DCM group, 10 patients with hypertrophic cardiac disease - HCD group, and 15 healthy volunteers - Control group). DCM group was subdivided in: DCM-1 (9 patients with recent disease onset) and DCM-2 (8 patients with chronic DCM). The % CD4+/CD25+ T-lymphocytes were analyzed by double fluorescence flow cytometry both ex vivo and after phytohaemagglutinin (PHA)-cultures with/without 5 and 10 microgr of human cardiac myosin. The cytokines were measured using Enzyme-Linked Immunosorbant Assay (ELISA) method. RESULTS Ex vivo analysis: In DCM group, CD4+/CD25+ T-cells significantly increased compared to other groups (p<0.05), due exclusively to DCM-2 subgroup (p=0.019). In PHA cultures in DCM-2 subgroup CD4+/CD25+ T-lymphocytes were significantly increased compared to all other groups (p<0.001). The addition of myosin in the cultures of DCM-2 subgroup maintained the same result. In cultures supernatants in DCM-2 subgroup, IL-2 levels were impressively increased compared to DCM-1 subgroup (p=5.91x10-6), HCD and Control groups (p<0.001). Addition of antigen decreased significantly IL-2 levels in DCM-2 subgroup (p=0.01). IFN-γ levels followed the same pattern of alterations. IL-10 levels were significantly increased in both DCM subgroups compared to HCD and Control groups (p<0.05). CONCLUSIONS Increased peripheral CD4+/CD25+ T-cells found in chronic DCM could be a useful prognostic marker in DCM progress. Increased synthesis of IL-2 and IFN-γ and varying IL-10 levels reflects a Th1 pattern of immune response during chronic disease and implies active cellular immunity process, related to poor prognosis. Thus, analysis of the Th1/Th2 phenotype may be useful in disease monitoring in patients with DCM. This paper is a part of PhD thesis. It has been published at the abstract book of the Acute Cardiac Care congress 2010.