ABSTRACT
Several CD4+ T helper (Th) cell subsets are shown to play a role in atherosclerotic lesion formation and progression. We investigated the frequencies of IL-17 and IFN-γ producing CD4+ T-cell subsets in the peripheral blood mononuclear cells (PBMCs) of 10 patients with atherosclerosis and 6 individuals with normal/insignificant coronary artery disease. Th1 and Th17 memory and effector T-cells were enumerated by flowcytometry and correlated with the clinical data and lipid profiles of the subjects. We found the ex-vivo (P=0.0001) and in-vitro production of IL-17 (P=0.001) but not IFN-γ by CD4+ memory T-cells of patients. CD45RO+ memory cells were the major producers of IL-17 and the CD4+CD45RO+PD-1- T-cells of the patients produced higher levels of IFN-γ than controls (P=0.02). Positive correlations between the frequency of CD4+CD45RO+IL-17+IFN-γ- T-cells and serum LDL-C (P=0.007), triglyceride (P=0.02), and systolic (P=0.001) and diastolic (P=0.009) blood pressures (BP) were found. The frequency of CD4+CD45RO+IL-17-IFN-γ- T-cells, which was higher in controls than patients, showed negative correlations with the serum LDL-C (P=0.01) and triglyceride (P=0.02) levels and systolic (P=0.003) and diastolic (P=0.01) BPs. The ex-vivo Th17 deviation of memory T-cells in atherosclerosis and high PD-1 expression are associated with the correlates of atherogenesis such as LDL, TG, and BP.
Subject(s)
Atherosclerosis/genetics , Cholesterol, LDL/blood , Immunologic Memory/genetics , Interleukin-17/immunology , Leukocyte Common Antigens/immunology , Th17 Cells/immunology , Adult , Atherosclerosis/blood , Atherosclerosis/immunology , Atherosclerosis/pathology , Blood Pressure , CD4 Antigens/genetics , CD4 Antigens/immunology , Case-Control Studies , Diastole , Female , Flow Cytometry , Gene Expression Regulation , Humans , Immunophenotyping , Interferon-gamma/genetics , Interferon-gamma/immunology , Interleukin-17/genetics , Leukocyte Common Antigens/genetics , Male , Middle Aged , Programmed Cell Death 1 Receptor/genetics , Programmed Cell Death 1 Receptor/immunology , Signal Transduction , Systole , Th1 Cells/immunology , Th1 Cells/pathology , Th17 Cells/pathology , Triglycerides/bloodABSTRACT
We investigated PD-1 levels on VZV-specific CD8+ T-cells of patients with zoster and the effect of PD-1 on the telomerase activity. CD3, CD8, CD137 and PD-1 expressions were analyzed on PBMCs from 9 symptomatic and 5 asymptomatic individuals. The effect of PD-1 blockade at the time of stimulation on the telomerase activity of non-senescent CD57-CD45RO+CD8+CD3+ memory T-cells was evaluated. PD-1 was elevated on CD8+ T-cells in patients. The frequency of PD-1+ and CD137- cells in total CD3+CD8+ T cells of patients was elevated compared to controls. Telomerase activity of non-senescent memory T-cells was lower than that of controls. Blockade of PD-1 at the time of stimulation increased telomerase activity of non-senescent memory T-cells, accompanied by increased CD137 expression. Low telomerase activity of the patients with reactivated zoster could be partially overcome by blocking PD-1 pathway.
