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Regulatory T Cells in Inflammation
Regulatory T-cells are essential components of the immune system, and several different subsets of regulatory T-cells have been described. Considerable regulatory function has been attributed to the CD4+CD25+ T-cell subset. These cells act by suppressing adaptive and possibly innate immune responses thereby maintaining or restoring the balance between immunity and tolerance. The suppressive effects of CD4+CD25+ regulatory T-cells are cell-contact dependent. Recent developments and viewpoints in the field of CD4+CD25+ regulatory T-cells as well as the potential use of regulatory T-cells in immunotherapy of inflammatory diseases are discussed in this volume. By linking data from experimental models with recent findings from the clinic, this book will be of interest to immunologists and other biomedical researchers as well as clinicians interested in the regulation and manipulation of the immune response during inflammatory disease.
Molecular Mechanisms of Dendritic Cell-Mediated Immune Tolerance and Autoimmunity
Dendritic cells (DCs) play a critical role in immune system, as they are necessary both for innate and adaptive immunity. According to their function, dendritic cells can be classified in immune tolerogenic or inflammatory DCs. DCs have been shown to regulate T cell-mediated immune responses and lead to immune tolerance and autoimmunity. For example, immune-tolerogenic DCs facilitate the development of regulatory T cells and inhibit T helper 17-mediated autoimmunity in mice with experimental autoimmune encephalomyelitis. Moreover, inflammatory DCs activate CD8+ and CD4+ T cells and elicit T cell-mediated inflammatory immune responses in vivo. However, the molecular and cellular mechanisms underlying DC-mediated immune tolerance and autoimmunity are still obscure.
Immune Interactions during the Reproductive Cycle
Mammalian pregnancy represents a unique immunological riddle in that the mother does not reject her allogeneic fetus. In part this is largely due to a general sequestration or diminution of T cell activity, and an increased involvement of the innate immune system. The field of immunology is concerned primarily with how innate and adaptive mechanisms collaborate to protect vertebrates from infection. Although many cellular and molecular actors have evidently important roles, antibodies and lymphocytes are considered to be the principal players. Yet despite their importance, it would be definitely simplistic to conclude that they are solely essential for immunity overall. A major distinction b...
Novel Therapies for Tolerance Induction in Solid Organ and Bone Marrow Transplantation
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Searching for Immune Tolerance Manipulating New Molecules and Exploiting New Concepts on Lymphocyte Biology
The break on immune tolerance is a common point between autoimmune diseases and the uncontrolled effector immune responses against allo-antigens in transplantation. Among the past years, several approaches to restore a suppressive immune state have included the targeting of co-stimulatory/inhibitory molecules on immune cells, the promotion or blockade of pivotal cytokines, and the extensive study on how to isolate and expand suppressive cells with the purpose to re-infuse them in patients. To date, the availability of new technologies has permitted to learn, in a more detailed way, the immune mechanisms carried out by suppressive lymphocytes, together with the identification of new potential...
Genetic Basis of Tolerance Induction Defects Underlying the Development of Autoimmune Pathologies
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The Molecular Mechanisms of Regulatory T cell Immunosuppression
Ever since Regulatory T cells (T-Regs) were first defined as peripheral CD4+ T cells that express the interleukin-2 (IL-2) receptor alpha chain (IL-2Ra), there have been intensive efforts to determine the molecular mechanisms whereby this minor subset of CD4+ T cells (~ 5-10%) nonspecifically suppresses all potential effector T cells, whether reactive to self or non-self antigens. Multiple possible molecular mechanisms have been implicated, including the scavenging of IL-2 via the expression of high densities of IL-2Rs, the inhibition of antigen presentation via CTLA-4 molecules leading to decreased IL-2 production, the activation of intracellular cAMP thereby suppressing both IL-2 productio...
