Profound Reduction in T-helper (Th) 1 lymphocytes in Peripheral Blood from Patients with Concurrent Type 1 Diabetes and Graves' Disease

Abstract

Type 1 diabetes likely is mediated by T-helper (Th) 1 lymphocytes, while Graves' disease may involve Th2 predominance. We investigated the balance between Th1 and Th2 cells and between Th1- and Th2-associated chemokine receptor expression on peripheral lymphocytes in subjects including patients with coexisting type 1 diabetes and Graves' disease. Peripheral blood mononuclear cells of all subjects were examined by flow cytometry for intracellular cytokines (IFN-gamma for Th1; IL-4 for Th2) and expression of the chemokine receptors CXCR3 (Th1-associated) and CCR4 (Th2-associated). Plasma concentrations of interferon-inducible protein (IP)-10, a CXCR3 ligand, and thymus and activation-regulated chemokine (TARC), a CCR4 ligand, were measured by enzyme-linked immunosorbent assays. IFN-gamma producing-T lymphocytes were significantly fewer in patients with coexisting type 1 diabetes and Graves' disease (12.4 +/- 6.8%, n = 6) than in healthy control subjects (19.9 +/- 4.1%, n = 6; P < 0.01) or patients with type 2 diabetes (19.1 +/- 4.5%, n = 5; P < 0.05). We found no significant difference in IFN-gamma-producing T lymphocytes between healthy controls and patients with only type 1 diabetes (n = 8) or Graves' disease (n = 5). Plasma IP-10 concentrations were significantly higher in patients with coexisting type 1 diabetes and Graves' disease than in control subjects (106.3 +/- 30.48 vs. 66.7 +/- 25.3 pg/ml, P = 0.0343). Considering only patients with type 1 diabetes alone, duration of diabetes correlated positively with IFN-gamma-producing T lymphocytes (r = 0.773, P = 0.0242) and the ratio of CXCR3 to CCR4 receptor expression (r = 0.947, P = 0.0004). In conclusion, Th1-associated T lymphocytes were fewer in peripheral blood from patients having both type 1 diabetes and Graves' disease than in those with either disease alone. Numbers of peripheral Th1 lymphocytes increased with increasing time from onset of type 1 diabetes in patients with type 1 diabetes alone.