CD4+IL-21+T cells are correlated with regulatory T cells and IL-21 promotes regulatory T cells survival during HIV infection.

INTRODUCTION: IL-21 enhances T and natural killer cells survival and antiviral functions without promoting T cell activation during HIV infection, which makes it a better adjuvant in anti-HIV immunotherapy. Due to the pleiotropy and redundancy of cytokines, it is vital to have a comprehensive knowledge of the role of IL-21 in the regulation of immune responses. Regulatory T cells (Tregs) play an important role in immune regulation and are a determinant of immune therapeutic efficacy in certain circumstances. In this study, we explored the direct effect of IL-21 on Tregs during HIV infection, which has not been addressed before. METHODS: Thirty-four HIV treatment-naïve patients were enrolled and the relationship between CD4+IL-21+T cells and Tregs were studied. The effects of IL-21 on CD4+CD25+CD127low Tregs' apoptosis, proliferation, and CTLA-4 and TGF-ß expression in HIV-infected patients was investigated and compared with the effect of other common γ-chain cytokines. RESULTS: We found the percentage and absolute numbers of CD4+IL-21+T cells were positively related to the frequency or absolute numbers of CD4+CD25+ or CD4+CD25+CD127low Tregs. Compared with the media-alone control, IL-21, IL-7, and IL-15 could significantly reduce apoptosis of Tregs (p<0.05). IL-21 did not promote the proliferation of Tregs as compared with media alone, while IL-2, IL-7, and IL-15 could significantly increase the proliferation of Tregs (p<0.05). IL-21 enhanced CTLA-4 expression by Tregs (p<0.05), but could not induce TGF-ß secretion of Tregs from HIV infected patients. There were no significant differences of the fold induction of apoptosis, proliferation, or CTLA-4 and TGF-ß expression by Tregs from HIV-infected patients and normal controls after IL-21 treatment. In vitro experiment showed that pretreatment with IL-21 significantly enhanced the suppressive effect of Tregs on CD8+ T cells' IFN-γ expression. CONCLUSION: We conclude that IL-21 promotes the survival and CTLA-4 expression of Tregs and enhanced the suppressive capacity of Tregs during HIV infection. These results broaden the understanding of HIV pathogenesis and provide critical information for HIV interventions.

Identification of heat shock cognate protein 70 gene (Alhsc70) of Apolygus lucorum and its expression in response to different temperature and pesticide stresses.

Heat shock cognate protein 70 (Hsc70) is a very important stress-resistance protein of insects against environmental stresses. We employed fluorescent real-time quantitative polymerase chain reaction and Western-blot techniques to analyze the transcriptional and translational expression profiles of AlHSC70 under extreme temperature (4°C and 40°C) or 4 pesticide stresses in Apolygus lucorum. The results showed that the expression of AlHSC70 were significantly induced by cyhalothrin or extremely high temperature (40°C) in both transcriptional and translational levels (P < 0.05), while the transcriptional and translational level of AlHSC70 decreased significantly in treatments of chlorpyrifos or extreme cold temperature (4°C) (P < 0.05). Moreover, after Apolygus lucorum treated by imidacloprid or emamectin benzoate, the expression of AlHSC70 was only up-regulated significantly at the transcriptional level (P < 0.05), although obviously up-regulated at the translational level of AlHSC70. Therefore, this study confirmed that the Alhsc70 gene played important roles in response to both temperature and pesticide stresses, especially for cyhalothrin or extremely high temperature (40°C). In addition, the significant polynomial regression correlations between temperature and the Alhsc70 expression level were shown in all the nymph and adult stages (P < 0.01), indicating temperature was an important factor to affect the relative expression of Alhsc70.

Molecular and functional characterization of the ecdysone receptor isoform-A from the cotton mirid bug, Apolygus lucorum (Meyer-Dür).

We cloned the cDNA of the ecdysone receptor (EcR) isoform-A from the mirid bug, Apolygus lucorum (AlEcR-A). The AlEcR-A cDNA has an open reading frame of 1410 bp with a conserved sequence of approximately 20 amino acids at the carboxyl-end of its A/B-specific domain. Phylogenetic analysis showed that AlEcR-A is very similar to the EcR-A genes of other Hemiptera species. AlEcR-A mRNA was detected at all developmental stages of A. lucorum with peaks correlating to ecdysteroid pulses. AlEcR-A was also expressed in all analyzed tissues with maximum expression in the epidermis and fat body. An AlEcR-A mRNA of size 1.8 kb was detected in all tissues by northern blot analysis. We investigated the functions of AlEcR-A in A. lucorum growth and development using RNAi in vivo. Weights of fifth instar nymphs were significantly decreased in insects treated with AlEcR-A specific anti-sense RNA. Mortality from third instar nymphs to adults increased significantly along with a significant increase in instar duration.

Relationship between adiponectin and testosterone in patients with type 2 diabetes.

INTRODUCTION: This study was designed to investigate the relationship between serum adiponectin and testosterone in patients with type 2 diabetes. MATERIALS AND METHODS: Serum level of adiponectin and testosterone were prospectively measured in 65 patients with type 2 diabetes and in 20 healthy subjects. Testosterone was determined by the radio-immunoassay whereas adiponectin levels were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: The average serum testosterone did not differ between the diabetes and the control group, but the average adiponectin in the diabetes group was lower (14.6 (14.2-15.0) vs. 24.3 (24.05-24.55) ng/mL, P = 0.001). In the diabetes group, the serum adiponectin level in patients with renal dysfunction (22.3 (21.5-23.1) ng/mL) was higher than in patients with no complications (12.1 (11.45-12.75) ng/mL) and than in patients with coronary artery disease (11.2 (10.25-12.15) ng/mL) (P = 0.009). Univariate correlation analysis showed an inverse weak correlation between adiponectin and testosterone concentrations in male diabetic patients (r = -0.27, P = 0.009). There was no significant correlation between adiponectin and testosterone in female patients (r = -0.05, P = 0.167). CONCLUSIONS: We conclude that patients with type 2 diabetes have lower serum adiponectin concentration than healthy individuals, and that there is a weak inverse correlation between adiponectin and testosterone serum concentrations in male diabetics.