A High Frequency of Peripheral Blood IL-22(+) CD4(+) T Cells in Patients With New Onset Type 2 Diabetes Mellitus.

BACKGROUND: This study is aimed at investigating the frequency of different functional IL-22(+) CD4(+) T cells in Chinese patients with type 2 diabetes mellitus (T2DM). METHODS: The frequency of circulating IFN-γ+IL-17-IL-22-CD4(+) (Th1), IFN-γ-IL-17A+IL-22-CD4(+) (Th17), and IFN-γ-IL-17A-IL-22(+) CD4(+) (Th22), and other subsets of IL-22(+) CD4(+) T cells in 31 patients with new onset T2DM and 16 healthy controls was characterized by flow cytometry. The levels of serum IL-22, IL-17, IFN-γ, insulin C-peptide, hemoglobin A1c (HbA1c), fasting plasma glucose, and insulin were examined. RESULTS: The frequency of Th1, Th17, Th22, IFN-γ(+) IL-17(-) IL-22(+) , and IFN-γ(-) IL-17(+) IL-22(+) CD4(+) T cells and the concentrations of IL-22, but not IL-17 and IFNγ, in the patients were significantly higher than controls. The percentages of Th22 cells were correlated positively with the frequency of IFN-γ(-) IL-17(+) IL-22(+) CD4(+) T cells, the values of body mass index (BMI) and homeostatic model assessment insulin resistance (HOMA-IR), and the levels of serum IL-22 in those patients. CONCLUSION: Our data suggest that IL-22(+) CD4(+) T cells may contribute to the early process of T2DM.

A higher frequency of circulating IL-22(+)CD4(+) T cells in Chinese patients with newly diagnosed Hashimoto's thyroiditis.

BACKGROUND: IL-22 and IL-17A are implicated in the pathogenesis of autoimmune diseases. However, the role of IL-22(+) and IL-17A(+) CD4(+) T cells in the pathogenesis of Hashimoto's thyroiditis (HT) is not fully understood. This study investigates serum IL-22 and IL-17A levels and determines the frequency of circulating IL-22(+) CD4(+) T cells in HT patients to understand their roles in the pathogenesis of HT. METHODS: The levels of serum IL-22, IL-17A and IFN-γ and the frequency of circulating IL-22(+)CD4(+) and IL-17A(+)CD4(+) T cells in 17 HT patients and 17 healthy controls (HC) were determined by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The levels of serum free triiodothyronine (FT4), free thyroxine (FT3), thyroid stimulating hormone (TSH), anti-thyroid peroxidase (TPO) and anti-thyroglobulin antibodies (TgAb) by chemiluminescent enzyme immunoassay and radioimmunoassay. RESULTS: The percentages of circulating IL-22(+)CD4(+) and IL-17(+)CD4(+) T cells (p<0.0001, p<0.0001) and the levels of serum IL-22, IL-17A and IFN-γ (p<0.0001, p<0.0001, p = 0.0210) in the HT patients were significantly higher than that in the HC. The percentages of IL-22(+)CD4(+) T cells were positively correlated with Th17 cells (r = 0.8815, p<0.0001) and IL-17A(+)IL-22(+)CD4(+) T cells (r = 0.8914, p<0.0001), but were negatively correlated with Th1 cells (r = -0.6110, p<0.0092) in the HT patients. The percentages of Th22 cells, Th17 cells and IL-17A(+)IL-22(+)CD4(+) T cells were negatively correlated with the levels of serum TSH in the HT patients (r = -0.8402, p<0.0001; r = -0.8589, p<0.0001; r = -0.8289 p<0.0001, respectively). CONCLUSIONS: A higher frequency of circulating IL-22(+)CD4(+) and IL-17A(+)CD4(+) T cells may be associated with the development of HT in Chinese patients.

A high frequency of peripheral blood NKG2D+NK and NKT cells in euthyroid patients with new onset hashimoto's thyroiditis--a pilot study.

Hashimoto's thyroiditis (HT) is a T cell-mediated autoimmune disease. However, little is known about the role of different subsets of natural killer (NK) and natural killer T (NKT) cells at the early stage of the HT process. A total of 45 euthyroid patients with new onset HT and 40 age/gender-matched healthy controls (HC) were examined for the frequency of different subsets of NK and NKT cells and their function by flow cytometry. In comparison with that in HC, significantly higher percentages of peripheral blood CD3-CD56+ NK, NKG2D+, NKp30+ NK and NKT cells, but significantly lower percentages of NKG2A+, KIR2DL3+ inhibitory NK and NKT cells were detected in the HT patients. Furthermore, the percentages of NKG2D+ NK cells were correlated positively with the concentrations of serum anti-thyroid peroxidase antibody (TPOAb) in the HT patients. Moreover, the percentages of inducible IFN-γ and CD107a+ NK cells in the HT patients were significantly higher than those in HC. Our data suggest that activated NK cells may participate in the early pathogenic process of HT.

A high frequency of circulating th22 and th17 cells in patients with new onset graves' disease.

T-helper (Th) 22 and Th17 cells are involved in the pathogenesis of autoimmune diseases. However, their roles in the pathogenesis of Graves'disease (GD) are unclear. This study is aimed at examining the frequency of peripheral blood Th22, Th17, and Th1 cells and the levels of plasma IL-22, IL-17, and IFN-γ in patients with GD. A total of 27 patients with new onset GD and 27 gender- and age-matched healthy controls (HC) were examined for the frequency of peripheral blood Th22, Th17, and IFN-γ cells by flow cytometry. The concentrations of plasma IL-22, IL-17, and IFN-γ were examined by enzyme-linked immunosorbent assay. The levels of serum TSHR antibodies (A-TSHR), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) were examined by radioimmunoassay and chemiluminescent assay, respectively. The levels of serum TSAb were examined by enzyme-linked immunosorbent assay. In comparison with those in the HC, significantly elevated percentages of Th22 and Th17 cells, but not Th1 cells, and increased levels of plasma IL-22 and IL-17, but not IFN-γ, were detected in GD patients (P<0.0001, for both). The percentages of both Th22 and Th17 cells and the levels of plasma IL-22 and IL-17 were correlated positively with the levels of serum TSAb in GD patients (r = 0.7944, P<0.0001; r = 0.8110, P<0.0001; r = 0.7101, p<0.0001; r = 0.7407, p<0.0001, respectively). Th22 and Th17 cells may contribute to the pathogenesis of GD.

High frequency of activated natural killer and natural killer T-cells in patients with new onset of type 2 diabetes mellitus.

Chronic low-grade inflammation is crucial for the development of insulin resistance and type 2 diabetes mellitus (T2DM), and immunocompetent cells, such as T-cells, B-cells, mast cells and macrophages, regulate the pathogenesis of T2DM. However, little is known about the role of natural killer (NK) and natural killer T (NKT) cells in the pathogenic process of T2DM. A total of 16 patients with new onset T2DM and nine healthy subjects were recruited, and the frequency of peripheral blood activated and inhibitory NK and NKT cells in individual subjects was determined by flow cytometry. The frequency of spontaneous and inducible interferon gamma (IFN-γ) and CD107a(+) NK cells was further examined, and the potential association of the frequency of NK cells with clinical measures was analyzed. While there was no significant difference in the frequency of peripheral blood NK and NKT cells between patients and controls, the frequency of NKG2D(+) NK and NKT cells in patients was significantly higher than those in the controls (P = 0.011). In contrast, the frequency of NKG2A(+) and KIR2DL3(+) inhibitory NK and NKT cells in patients was significantly lower than those in the controls (P = 0.002, P < 0.0001, respectively). Furthermore, the frequencies of NKG2D(+) NK cells were correlated significantly with the values of body mass index in patients. Moreover, the frequencies of spontaneous and inducible CD107a(+), but not IFN-γ-secreting, NK cells in patients were significantly higher than those in the controls (P < 0.004, P < 0.0001). Our data indicated that a higher frequency of activated NK cells may participate in the obesity-related chronic inflammation involved in the pathogenesis of T2DM.

Patients with chronic hepatitis C express a high percentage of CD4(+)CXCR5(+) T follicular helper cells.

BACKGROUND: T follicular helper (T(FH)) cells are a subpopulation of T-helper cells which regulate humoral immune responses. The role of T(FH) cells in viral infection is unclear. This study examined the possible involvement of CD4(+)CXCR5(+) T(FH) cells in chronic hepatitis C (HCV) infection. METHODS: The percentages of peripheral blood CD4(+)CXCR5(+) T(FH) cells, inducible T-cell costimulator cells, and/or programmed death 1-positive CD4(+)CXCR5(+) T(FH) cells in 39 HCV-infected patients, 12 patients with spontaneously resolved HCV infection (SR-HCV), and 12 healthy controls were characterized by flow cytometry analysis. The subjects' serum HCV RNA loads and alanine aminotransferase and aspartate aminotransferase levels were measured. The potential association of the percentage of peripheral CD4(+)CXCR5(+) T(FH) cells with clinical data was analyzed. RESULTS: Higher percentages of peripheral blood CD4(+)CXCR5(+) T(FH) cells were found in SR-HCV and HCV-infected patients as compared with healthy controls. Interestingly, a statistically significant negative correlation was found between the percentage of CD4(+)CXCR5(+) T(FH) cells and the HCV RNA load. CONCLUSIONS: These data suggest that CD4(+)CXCR5(+) T(FH) cells may participate in HCV-related immune responses. Increased T(FH) cells in peripheral blood may help to control HCV infection.