No abstract

HCV infection has a severe course of disease in HIV/HCV co-infection and in liver transplant recipients. However, the mechanisms involved remain unclear. Here, we evaluated functional profiles of HCV-specific T-cell responses in 86 HCV mono-infected patients, 48 HIV/HCV co-infected patients and 42 liver transplant recipients. IFN-c and IL-2 production and ability of CD4 and CD8 T cells to proliferate were assessed after stimulation with HCVderived peptides. We observed that HCV-specific T-cell responses were polyfunctional in HCV mono-infected patients, with presence of proliferating single IL-2-, dual IL-2/IFN-c and single IFN-c-producing CD4 1 and dual IL-2/IFN-c and single IFN-c-producing CD8 1 cells. In contrast, HCV-specific T-cell responses had an effector profile in HIV/HCV coinfected individuals and liver transplant recipients with absence of single IL-2-producing HCV-specific CD4 1 and dual IL-2/IFN-c-producing CD8 1 T cells. In addition, HCV-specific proliferation of CD4 1 and CD8 1 T cells was severely impaired in HIV/HCV co-infected patients and liver transplant recipients. Importantly, ''only effector'' T-cell responses were associated with significantly higher HCV viral load and more severe liver fibrosis scores.Ã These two authors contributed equally to this work. Therefore, the present results suggest that immune-based mechanisms may contribute to explain the accelerated course of HCV infection in conditions of HIV-1 co-infection and liver transplantation.

Common variable immunodeficiency (CVID) is characterized by abnormally low levels of antibodies in the blood and dysfunctional immune cells called CD4+ T cells. Perreau et al. now show evidence that bacteria-fighting CD4+ T cells in these patients are in a state of exhaustion due to a constant leakage of normal gut bacteria into the bloodstream, possibly due to insufficient antibody levels.

Biologic agents have substantially advanced the treatment of immunological disorders, including chronic inflammatory and autoimmune diseases. However, these drugs are often associated with adverse events (AEs), including allergic, immunological and other unwanted reactions. AEs can affect almost any organ or system in the body and can occur immediately, within minutes to hours, or with a delay of several days or more after initiation of biologic therapy. Although some AEs are a direct consequence of the functional inhibition of biologic-agent-targeted antigens, the pathogenesis of other AEs results from a drug-induced imbalance of the immune system, intermediary factors and cofactors, a complexity that complicates their prediction. Herein, we review the AEs associated with biologic therapy most relevant to rheumatic and immunological diseases, and discuss their underlying pathogenesis. We also include our recommendations for the medical management of such AEs. Increased understanding and improved risk management of AEs induced by biologic agents will enable better use of these versatile immune-response modifiers.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by a loss of tolerance to multiple endogenous antigens. SLE etiology remains largely unknown, despite recent insight into the immunopathogenesis of the disease. T cells are important in the development of the disease by amplifying the immune response and contributing to organ damage. Aberrant signaling, cytokine secretion and tissue homing displayed by SLE T cells have been extensively studied and the underlying pathogenic molecular mechanisms are starting to be elucidated. T-cell targeted treatments are being explored in SLE patients. This review is an update on the T-cell abnormalities and related therapeutic options in SLE.