Adiponectin inhibits oxidization-induced differentiation of T helper cells through inhibiting costimulatory CD40 and CD80

Adiponectin is a multifunctional adipokine that has several oligomeric forms in the blood stream, which broadly regulates innate and acquired immunity. Therefore, in this study, we aimed to observe the differentiation of T helper (Th) cells and expression of costimulatory signaling molecules affected by adiponectin. The mRNA and protein expression levels of adiponectin and its receptors in oxidized low density lipoprotein cholesterol-treated endothelial cells were assayed by real time PCR and immunofluorescence. The endothelial cells were then treated with adiponectin with or without adipoR1 or adipoR2 siRNA and co-cultured with T lymphocytes. The distribution of Th1, Th2 and Th17 subsets were assayed by flow cytometry. The effects of adiponectin on costimulatory signaling molecules HLA-DR, CD80, CD86 and CD 40 was also assayed by flow cytometry. The results showed that endothelial cells expressed adiponectin and its receptor adipoR1 and adipoR2, but not T-cadherin. Adiponectin suppressed Th1 and Th17 differentiation through adipoR1 receptor, contributed to the inhibition of CD80 and CD40, and inhibited differentiation of Th1 and Th17 by inhibiting antigen presenting action.

Costimulatory molecule B7-H1 on the immune escape of bladder cancer and its clinical significance / 华中科技大学学报（医学）（英德文版）

B7-H1, a recently described member of the B7 family of costimulatory molecules, is thought to be involved in tumor immune escape by inducing T-cell apoptosis. In order to investigate the relationship between B7-H1 and immune escape of bladder cancer, B7-H1 expression in 50 cases of bladder cancer was detected by using immunohistochemical method. Survival curves were constructed using the Kaplan-Meier method and independent prognostic factors were evaluated using the Cox regression model. Our results showed that the positive rate of B7-H1 immunostaining in normal bladder tissue and bladder cancer was 0 and 72% respectively. The expression of B7-H1 was strongly associated with the pathological grade, clinical stage and recurrence (P<0.05). The survival rate was significantly lower in patients with B7-H1 positive group than in those with B7-H1 negative group and multi-variable analysis revealed that B7-H1 could be regarded as an independent factor in evaluating the prognosis of bladder cancer. It is concluded that the expression of B7-H1 is strongly associated with neoplastic progression and prognosis of bladder cancer. The manipulation of B7-H1 may become a beneficial target for immunotherapy in human bladder cancer.

Expression of co-stimulatory molecules B7.1 & B7.2 on macrophages infected with various strains of Mycobacterium tuberculosis & its influence on T-cell apoptosis.

BACKGROUND & OBJECTIVE: Activation of T cells is mediated through two critical signals provided by activated macrophages. The first signal is triggered when T cell receptor (TCR) binds to the major histocompatibility antigen (MHC/Ag) complex. The second signal is the interaction of co-stimulatory molecules with their respective ligands on T cells for their activation and proliferation. We undertook this study to observe the modulation in B7.1 (CD80) and B7.2 (CD86) co-stimulatory molecules on Mycobacterium tuberculosis infected monocyte derived macrophages (MDM) and their role in T helper (Th1) cell apoptosis. METHODS: M. tuberculosis clinical strains (S7 and S10) and laboratory strains (H37Ra and H37Rv) were used to infect the MDMs. The modulation of apoptosis was assessed by treating T cells with anti-CD3 and anti-CD28 antibodies. The infected MDMs were co-cultured with autologous PPD pulsed T cells to ascertain the role of co-stimulatory molecules during infection. RESULTS: In infected MDMs, all strains on day 1 but only S7 on day 2 showed significant decrease (P<0.05) in B7.1 expression compared to uninfected. The expression levels of B7.2 were also low on day 1 in S7, S10 and H37Ra infected MDMs. The anit-CD3 induced apoptosis in PPD pulsed Tcells showed further reduction with anti-CD28 antibodies. However, the modulation observed in B7.1 expression in infected MDMs was not reflected in T cell apoptosis in co-culture experiments. INTERPRETATION & CONCLUSION: Our results confirmed the role of B7.1 in rescuing the activated Tcells from undergoing apoptosis. During infection when the expression of B7.1 is downregulated, other co-stimulatory molecules may take over its crucial role to confer protective immune response against M. tuberculosis.

Impaired responses of leukemic dendritic cells derived from a human myeloid cell line to LPS stimulation

Several myeloid leukemia-derived cells have been reported to possess the ability to differentiate into dendritic cells (DC). MUTZ-3, a myeloid leukemia cell line, responds to GM-CSF, IL-4 and TNF-alpha, and acquires a phenotype similar to immature monocyte-derived DC (MoDC). In the present study, MUTZ-3-derived DC (MuDC) showed high level expression of HLA class II molecules, CD80 and CD86, and were able to function as potent antigen presenting cells as previously reported. Interestingly, MuDC maturation was induced by CD40-mediated stimulation, but not by LPS stimulation. We analyzed CCR1, CCR7 and Toll-like receptor (TLR) expressions in MuDC, and measured IL-10 and IL-12 production after maturation stimuli. Although MuDC expressed the mRNA for TLR4, a major component of the LPS receptor system, they did not show an enhanced level of CCR7 or cytokine production after LPS stimulation. In contrast, they responded to CD40 stimulation, which resulted in increased levels of CD83, CD86 and CCR7. Moreover, while LPSstimulated MoDC could potently stimulate NK cells in a DC-NK cell co-culture, LPS-stimulated MuDC failed to stimulate primary NK cells. Taken together, our findings suggest that, although MuDC express TLR4, unlike TNF-alpha and IL-1beta, LPS does not stimulate MuDC to acquire mature phenotypes, and they may have impaired activity to initiate innate immune response.