The 60 kDa heat shock protein family, Hsp60, constitutes an abundant and highly conserved class of molecules that are highly expressed in chronic-inflammatory and autoimmune processes. Experimental autoimmune uveitis [EAU] is a T cell mediated intraocular inflammatory disease that resembles human uveitis. Mycobacterial and homologous Hsp60 peptides induces uveitis in ...

B-cell activation factor belonging to the tumor necrosis factor family (BAFF) is a major contributor to survival of B lymphocytes during development and maturation. A relationship between circulating BAFF levels and disease activity has been reported in patients with the autoimmune disease Systemic Lupus Erythematosus (SLE). Clinical trials targeting BAFF ...

BACKGROUND: An inflammatory insult following middle cerebral artery occlusion (MCAO) is associated with a predisposition to develop a deleterious autoimmune response to the brain antigen myelin basic protein (MBP). Induction of immunologic tolerance to brain antigens prior to MCAO prevents this deleterious autoimmune response and is associated with better functional ...

Systemic lupus erythematosus (SLE) is a complex autoimmune disease of unknown etiology that involves multiple interacting cell types driven by numerous cytokines and autoimmune epitopes. Although the initiating events leading to SLE pathology are not understood, there is a growing realization that dysregulated cytokine action on immune cells plays an ...

To protect against viral infection, the immune response is critically dependent on innate sensing mechanisms to provide rapid detection of pathogens and allow for the development of an appropriate adaptive immune response. Mounting evidence suggests that mechanistic differences in the sensing of viruses by the innate immune response can contribute ...

Nature has provided the developing immune system with several checkpoints important for the maintenance of tolerance and the prevention of autoimmunity. The regulatory mechanisms operating in the periphery of the system are mediated by subsets of regulatory cells, now considered principal contributors to peripheral tolerance. Regulatory T cells (Tregs) have ...

The immune system balances effector responses with tolerance, to protect the host from pathogens while minimizing local damage to tissue. An altered control of immune homeostasis can lead to loss of tolerance to self antigens in autoimmunity, or promote unwanted tolerance to tumor growth. This review focuses on the dual ...

CD4(+) T cells from the TCR transgenic TxA23 mouse recognize a peptide from the H/K-ATPase alpha-chain. When TxA23 CD4(+) thymocytes are differentiated into Th1, Th2, and Th17 lines, all three subpopulations induced autoimmune gastritis (AIG) upon transfer into nu/nu recipients. The induction of AIG by naive T cells or by ...

FoxP3(+) regulatory T cells (Tregs) protect against autoimmunity, type 1 diabetes (T1D) in particular, prompting the hypothesis that a deficiency in Tregs is a critical determinant of diabetes susceptibility in NOD mice. However, tests of this hypothesis have yielded contradictory results. We confirmed that NOD mice, compared with reference strains, ...

As the immune system develops, T cells are selected or regulated to become tolerant of self antigens and reactive against foreign antigens. In mice, the induction of such tolerance is thought to be attributable to the deletion of self-reactive cells. Here, we show that the human fetal immune system takes ...

Numerous cases of primary hypophysitis have been described over the past 25 years with, however, little insight into the cause(s) of this disease. In order to guide treatment, a better understanding of the pathogenesis is needed. We studied the pathogenesis of primary hypophysitis by analysing systematically the immune response at ...

Despite strong circumstantial evidence for the autoimmune hypothesis of narcolepsy, conventional immunological methods have failed to detect an autoantibody. This study investigated the real-time effects of narcoleptic immunoglobulins on a spontaneous colonic migrating motor complex (CMMC) preparation. IgG from patients with narcolepsy with cataplexy or healthy controls was added directly ...

The encounter with different environmental antigens during immune maturation from childhood through early adulthood could play a role in the development of autoimmune disease in individuals with a susceptible genetic background. Autologous haematopoietic stem cell transplantation (HSCT) is an experimental treatment for autoimmunity that could offer a second possibility to ...

Autoimmune diseases represent a major challenge for medical research. The aberrant self-recognition by the immune system leads to a range of pathologies for which cures have not been forthcoming. Treatments are commonly non-specific and often lead to unwanted side-effects. A number of strategies are currently being explored to tackle autoimmunity; ...

Recently, it has been shown that plasma cells secreting antibodies can be long lived and as such constitute an independent component of immunological memory. They are generated in the context of memory immune reactions and migrate to the bone marrow, where they persist for years and decades. Their survival is ...

The activation, expansion, and survival of regulatory T cells (Tregs) as well as the expression of their suppressive capacities result from distinct signaling pathways involving various membrane receptors and cytokines. Multiple studies have shown that thymus-derived naturally occurring Tregs constitutively express the forkhead/winged helix transcription factor FoxP3 in addition to ...

B lymphocytes contribute to immunity through organogenesis of secondary lymphoid organs, presentation of antigen to T cells, production of antibodies, and secretion of cytokines. Their roles in autoimmune diseases are complex. Clinical trials have shown that depleting B cells can significantly ameliorate such diseases, underlining the contributions of B cells ...

Interleukin 21 (IL21) belongs to a family of cytokines that bind to a composite receptor consisting of a private receptor (IL21R) and the common cytokine receptor gamma chain (gamma(C)). The IL21R is widely distributed on lympho-haematopoietic cells and IL21 impacts a number of cell types, including CD8+ memory T cells, ...

Regulatory T cells (Tregs) play an essential role in the induction and maintenance of peripheral tolerance as well as prevention of autoimmunity by limiting the strength of the immune response of effector T cells. Macrophages, a heterogeneous population of phagocytes and professional antigen presenting cells (APCs), can also exert suppressive ...

The study of interleukin-23 (IL-23) over the past 8 years has led to the realization that cellular immunity is far more complex than previously appreciated, because it is controlled by additional newly identified players. From the analysis of seemingly straightforward cytokine regulation of autoimmune diseases, many limitations of the established ...

Since a decade autologous stem cell transplantation (ASCT) is successfully performed to treat patients with severe autoimmune disease. However, the mechanism of action of this intervention remains largely unknown. Scarce data from animal studies and human clinical trials indicate that, besides extensive immune ablation, restoration of regulatory immune networks is ...

Advances in our understanding of autoimmunity and tumour immunity have led to improvements in immunotherapy for these diseases. Ironically, effective tumour immunity requires the induction of the same responses that underlie autoimmunity, whereas autoimmunity is driven by dysregulation of the same mechanisms that are involved in host defence and immune ...

Type 1 diabetes (T1D) is caused by autoimmune beta cell destruction. The early events triggering T1D and the forces that keep diabetic autoimmunity pancreas specific have been unclear. Our discovery that autoimmune islet destruction is not beta-cell-exclusive but includes cytotoxic T cell targeting of peri-islet glia, evoked the possibility that ...

Regulatory T (Treg) cells are emerging as key players in the regulation of different immune responses, thereby representing potential candidates for therapeutic interventions in a broad variety of immunological disorders. While the reduction or loss in function would be of benefit during the treatment of cancer, induction and/or expansion of ...

Systemic lupus erythematosus (SLE) is a common autoimmune disease with complex etiology. Recently, a possible role of apoptotic cells in its pathogenesis has been suggested. This study is to evaluate the expression of Fas antigen on peripheral blood lymphocytes (PBLs) in SLE, to determine whether membrane Fas (mFas) has a ...

B lymphocytes play a central role in the pathogenesis of autoimmunity, so that B cell suppression is considered a potential treatment option for immune-mediated diseases. Rituximab, a chimeric anti-human CD20 antibody, is the only anti-B cell biological agent presently under study for the treatment of autoimmune neuromuscular diseases. Isolated case ...

Forkhead box p3 (Foxp3)-expressing regulatory T cells are key mediators of peripheral tolerance suppressing undesirable immune responses. Ectopic expression of Foxp3 confers regulatory T cell phenotype to conventional T cells, lending itself to therapeutic use in the prevention of autoimmunity and transplant rejection. Here, we show that adoptive transfer of ...

Immune privilege has been considered for many years to be an interesting phenomenon associated with certain specialised tissues such as the eye and the brain. In recent years however, it has become clear that the active and passive mechanisms which underpin immune privilege are in fact a form of tissue-based ...

CD4+CD25+ regulatory T cells (Tregs) can influence various immune responses. Little is known about the effects of the Abl/Src kinase inhibitor dasatinib on Tregs which regulate anti-tumor/leukaemia immune responses. The present study demonstrated that dasatinib inhibited proliferation of Tregs and CD4+CD25- T cells in a dose-dependent manner, which was associated ...

Abdominal aortic aneurysms (AAAs) are a multifactorial degenerative vascular disorder. One of the defining features of the pathophysiology of aneurysmal disease is inflammation. Recent developments in vascular and molecular cell biology have increased our knowledge on the role of the adaptive and innate immune systems in the initiation and propagation ...

The heavy metal mercury is ubiquitously distributed in the environment resulting in permanent low-level exposure in human populations. Mercury can be encountered in three main chemical forms (elemental, inorganic, and organic) which can affect the immune system in different ways. In this review, we describe the effects of these various ...

Type 1 diabetes mellitus results from the progressive and specific autoimmune destruction of insulin-secreting pancreatic B-cells, which develops over a period of years and continues after the initial clinical presentation. The ultimate goal of therapeutic intervention is prevention or reversal of the disease by the arrest of autoimmunity and by ...

Producing a healthy immune system capable of defending against pathogens, while avoiding autoimmunity, is dependent on thymic selection. Positive selection yields functional T cells that have the potential to recognize both self and foreign antigens. Therefore, negative selection exists to manage potentially self-reactive cells. Negative selection results from the induction ...

Fcgamma receptors (FcgammaRs) on mononuclear phagocytes trigger autoantibody and immune complex-induced diseases through coupling the self-reactive immunoglobulin G (IgG) response to innate effector pathways, such as phagocytosis, and the recruitment of inflammatory cells. FcRgamma-based activation is critical in the pathogenesis of these diseases, although the contribution of FcgammaR-mediated calcium signaling ...

PURPOSE: Immune dysfunction is well documented in renal cell carcinoma (RCC) patients and likely contributes to tumor evasion. This dysfunction includes a shift from a type-1 to a type-2 T-cell cytokine response and enhanced T-regulatory (Treg) cell expression. Given the antitumor activity of select tyrosine kinase inhibitors such as sunitinib ...

Primary cicatricial alopecias (PCA) represent uncommon inflammatory disorders that result in permanent loss of scalp hair. Cutaneous autoimmunity, most prominently chronic cutaneous lupus erythematosus (CCLE), can result in this kind of scarring hair loss. The cosmetic disfigurement caused by PCA and the very unsatisfactory therapeutic options available to date all ...

Naturally occurring Foxp3+CD4+ regulatory T cells (Tregs) are essential for maintaining immunological self-tolerance and immune homeostasis. Here, we show that a specific deficiency of cytotoxic T lymphocyte antigen 4 (CTLA-4) in Tregs results in spontaneous development of systemic lymphoproliferation, fatal T cell-mediated autoimmune disease, and hyperproduction of immunoglobulin E in ...

Interferon gamma (IFNgamma) plays a central role in the immune response against infection and tumur immune surveillance. Its functions include not only activation of the host immune system to control microbial infections but also repression of autoimmune responses by turning on T-regulatory cells and increasing T effector cell apoptosis. Defects ...

Modulation of the developing immune system can occur following perinatal exposure to a number of immunotoxic compounds, including polyhalogenated hydrocarbons like 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD; dioxin), the most toxic of the congeners. Studies in rodents have shown immunologic effects from perinatal TCDD exposure are more severe and persistent than following exposure in ...

Cell death plays a pivotal role in development and homeostasis of multicellular organisms. Apoptosis represents the physiological and anti-inflammatory form of cell death. Advanced apoptosis and necrosis are rather pro-inflammatory. Several "find-me"- and "eat-me"-signals support the "swift and silent" removal of dying cells. If the highly controlled process of dying ...

Immunosenescence is defined as all the changes occurring in the immune system in the aged. Recent studies suggest that in older patients the immune system undergoes a functional remodelling. Two contrasting phenomena coexist in immunosenescence: the decreasing of immune response and the autoantibody production. Possible consequences are an increase of ...

Antiphospholipid syndrome (APS) is a clinical autoimmune disorder characterised by thrombosis, venous or arterial, and recurrent pregnancy morbidity in association with the persistence of antiphospholipid antibodies (aPL). The clinical variety of aPL ranges from asymptomatic individuals to those with multiple organ thromboses and failure developing over a short period, also ...

Tregs are important mediators of immune tolerance to self antigens, and it has been suggested that Treg inactivation may cause autoimmune disease. Therefore, immunotherapy approaches that aim to restore or expand autoantigen-specific Treg activity might be beneficial for the treatment of autoimmune disease. Here we report that Treg-mediated suppression of ...

Hashimoto thyroiditis can be partially reproduced in mice by immunization with thyroglobulin or, more recently, thyroperoxidase. This experimental autoimmune thyroiditis (EAT) model has been extensively characterized during early disease phases (up to d 35 after immunization). By extending the analysis of EAT to 100 d after immunization, we noted a ...

INTRODUCTION: The immune response is controlled by several inhibitory mechanisms. These mechanisms include regulatory T cells, which exist in multiple classes. Notable among these are Foxp3-expressing regulatory T cells (Treg), NKT cells, and Tr1 cells. Common to these mechanisms are inhibitory cytokines such as interleukin-10 and transforming growth factor-beta (TGF-beta). ...

Activation-induced cell death is a general mechanism of immune homeostasis through negative regulation of clonal expansion of activated immune cells. This mechanism is involved in the maintenance of self- and transplant tolerance through polarization of the immune responses. The Fas/Fas-ligand interaction is a major common executioner of apoptosis in lymphocytes, ...

Regulatory T cells (Tregs) play a vital role in maintaining homeostatic balance within the immune system. Tregs are required for mediating normal immune responses against pathogens and then terminating such responses when no longer required. However, Tregs also provide important regulation of autoimmune responses, specifically in preventing autoimmunity. They are ...

Several immune cell subsets contribute to the maintenance of peripheral tolerance by taking active participation in the networks that suppress autoreactive immune responses. There is ample evidence that CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) can have an important role in suppressing the production of autoimmune responses in animal models and in ...

Graves' disease, an autoimmune process associated with thyroid dysfunction, can also manifest as remodeling of orbital connective tissue. Affected tissues exhibit immune responses that appear to be orchestrated by resident cells and those recruited from the bone marrow through their expression and release of cytokines and surface display of cytokine ...

PURPOSE OF REVIEW: To discriminate the pathomechanims of autoimmunity from that of autoimmune tissue injury, for example, in systemic lupus erythematosus, with a special focus on the role of innate pathogen recognition receptors in lupus nephritis. RECENT FINDINGS: Toll-like receptors mediate immune activation upon the recognition of pathogens in different ...