Polarization of T-helper lymphocytes toward the Th2 phenotype in uremic patients

Abstract

T-helper (Th) lymphocytes consist of Th1 and Th2 subsets. Th1 cells are effectors of cell-mediated immunity and secrete interferon-[gamma ] (IFN-[gamma ]), which recruits new Th1 cells in cooperation with interleukin-12 (IL-12; produced by monocytes) and inhibits Th2 differentiation. Th2 cells produce IL-4 and IL-10, which inhibit IFN-[gamma ] secretion and cell immunity. We investigated whether the impaired immune response in uremia is associated with an altered balance of Th1/Th2. Peripheral-blood mononuclear cells (PBMCs) were collected from patients with chronic renal failure (CRF) on conservative treatment (CRF patients), patients with end-stage renal disease (ESRD) on regular hemodialy-sistherapy (ESRD-HD patients), and healthy controls (CON). CD4+ cells were isolated from PBMCs by negative selection using a magnetic labeling system. PBMCs and purified CD4+ cells were cultured in Iscove[apos ]s medium and Iscove[apos ]s medium plus mitogens (phytohemagglutinin and lipopolysaccharide). IFN-[gamma ], IL-12, IL-4, and IL-10 were measured in supernatant. The constitutive release of IL-4 and IL-10 by PBMCs and CD4+ cells of CRF and ESRD-HD patients was increased by five to eight times in comparison with CON (P [lt ] 0.001). Constitutive IFN-[gamma ] release by PBMCs of ESRD-HD patients was undetectable, although they secreted an increased amount of IL-12. Mitogen stimulated release of IFN-[gamma ] by PBMCs and CD4+ cells of CRF and ESRD-HD patients was blunted (average PBMCs:CON, 115.8 pg/2 [times ] 106 cells; CRF, 81.8 pg/2 [times ] 106 cells; ESRD-HD, 9.3 pg/2 [times ] 106 cells; CD4+ cells: CON, 358.0 pg/5 [times ] 105 cells; CRF, 165.4 pg/5 [times ] 105 cells; ESRD-HD, 43.5 pg/5 [times ] 105 cells). The ability of PBMCs of ESRD-HD patients to secrete IFN-[gamma ] was recovered after IL-4 and IL-10 neutralization. Uremia is associated with a prevalence of Th1 over Th2 cells and a configuration of cytokine network that depresses cell-mediated immunity. [copy ] 2001 by the National Kidney Foundation, Inc.