Suppressor CD4+ T cells expressing HLA-G are expanded in the peripheral blood from patients with acute decompensation of cirrhosis.

OBJECTIVE: Identifying components of immuneparesis, a hallmark of chronic liver failure, is crucial for our understanding of complications in cirrhosis. Various suppressor CD4+ T cells have been established as potent inhibitors of systemic immune activation. Here, we establish the presence, regulation and mechanism of action of a suppressive CD4+ T cell subset expressing human leucocyte antigen G (HLA-G) in patients with acute decompensation of cirrhosis (AD). DESIGN: Flow cytometry was used to determine the proportion and immunophenotype of CD4+HLA-G+ T cells from peripheral blood of 20 healthy controls (HCs) and 98 patients with cirrhosis (28 with stable cirrhosis (SC), 20 with chronic decompensated cirrhosis (CD) and 50 with AD). Transcriptional and functional signatures of cell-sorted CD4+HLA-G+ cells were delineated by NanoString technology and suppression assays, respectively. The role of immunosuppressive cytokine interleukin (IL)-35 in inducing this population was investigated through in vitro blockade experiments. Immunohistochemistry (IHC) and cultures of primary human Kupffer cells (KCs) were performed to assess cellular sources of IL-35. HLA-G-mediated T cell suppression was explored using neutralising antibodies targeting co-inhibitory pathways. RESULTS: Patients with AD were distinguished by an expansion of a CD4+HLA-G+CTLA-4+IL-35+ immunosuppressive population associated with disease severity, clinical course of AD, infectious complications and poor outcome. Transcriptomic analyses excluded the possibility that these were thymic-derived regulatory T cells. IHC analyses and in vitro cultures demonstrate that KCs represent a potent source of IL-35 which can induce the observed HLA-G+ phenotype. These exert cytotoxic T lymphocyte antigen-4-mediated impaired responses in T cells paralleled by an HLA-G-driven downregulation of T helper 17-related cytokines. CONCLUSION: We have identified a cytokine-driven peripherally derived suppressive population that may contribute to immuneparesis in AD.

Collaborative Learning Based Sybil Attack Detection in Vehicular AD-HOC Networks (VANETS).

Vehicular Ad-hoc network (VANET) is an imminent technology having both exciting prospects and substantial challenges, especially in terms of security. Due to its distributed network and frequently changing topology, it is extremely prone to security attacks. The researchers have proposed different strategies for detecting various forms of network attacks. However, VANET is still exposed to several attacks, specifically Sybil attack. Sybil Attack is one of the most challenging attacks in VANETS, which forge false identities in the network to undermine communication between network nodes. This attack highly impacts transportation safety services and may create traffic congestion. In this regard, a novel collaborative framework based on majority voting is proposed to detect the Sybil attack in the network. The framework works by ensembling individual classifiers, i.e., K-Nearest Neighbor, Naïve Bayes, Decision Tree, SVM, and Logistic Regression in a parallel manner. The Majority Voting (Hard and Soft) mechanism is adopted for a final prediction. A comparison is made between Majority Voting Hard and soft to choose the best approach. With the proposed approach, 95% accuracy is achieved. The proposed framework is also evaluated using the Receiver operating characteristics curve (ROC-curve).