Mechanisms of CD8+ T cell peripheral tolerance to our own antigens (original) (raw)
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Induction of peripheral CD4+ T-cell tolerance and CD8+ T-cell cross-tolerance by dendritic cells
European Journal of Immunology, 2009
DC can present and cross-present self-antigens to autoreactive CD4 1 and CD8 1 T cells, respectively, and incapacitate them by inducing anergy, deletion or converting them into Treg. In this review, we summarize the recent progress in immune tolerance research, which has been achieved by employing antigen-and TCR-transgenic mice. We cover the numerous discoveries that have furthered our knowledge of the DC subsets and maturation pathways involved in tolerance; the signals, such as CD70, TGF-b, B7-H1/PD-L1, which dictate the decision between immunity and tolerance; and the in vivo role of DC in the maintenance of CD4 1 T-cell tolerance and CD8 1 T-cell cross-tolerance.
Journal of Experimental Medicine, 2002
We previously described a mechanism for the maintenance of peripheral self-tolerance. This involves the cross-presentation of tissue-associated antigens by a bone marrow–derived cell type that stimulates the proliferation and ultimate deletion of self-reactive CD8 T cells. This process has been referred to as cross-tolerance. Here, we characterize the elusive cell type responsible for inducing cross-tolerance as a CD8α+ dendritic cell (DC). To achieve this aim, transgenic mice were generated expressing yellow fluorescent protein (YFP) linked to CTL epitopes for ovalbumin and glycoprotein B (gB) of herpes simplex virus under the rat insulin promoter (RIP). Although tracking of YFP was inconclusive, the use of a highly sensitive gB-specific hybridoma that produced β-galactosidase on encounter with antigen, enabled detection of antigen presentation by cells isolated from the pancreatic lymph node. This showed that a CD11c+CD8α+ cell was responsible for cross-tolerance, the same DC subs...
Journal of Leukocyte Biology, 2007
Dendritic cells (DC), professional antigen-presenting cells of the immune system, exert important functions both in induction of T cell immunity, as well as tolerance. It is well established that the main function of immature DC (iDC) in their in vivo steady-state condition is to maintain peripheral tolerance to self-antigens and that these iDC mature upon encounter of so-called danger signals and subsequently promote T cell immunity. Previously, it was believed that T cell unresponsiveness induced after stimulation with iDC is caused by the absence of inflammatory signals in steady-state in vivo conditions and by the low expression levels of costimulatory molecules on iDC. However, a growing body of evidence now indicates that iDC can also actively maintain peripheral T cell tolerance by the induction and/or stimulation of regulatory T cell populations. Moreover, several reports indicate that traditional DC maturation can no longer be used to distinguish tolerogenic and immunogenic properties of DC. This review will focus on the complementary role of dendritic cells in inducing both tolerance and immunity, and we will discuss the clinical implications for dendritic cell-based therapies. J. Leukoc. Biol. 82: 1365-1374; 2007.
Peripheral Tolerance of CD8 T Lymphocytes
Immunity, 2005
Furthermore, a recent report dem-1 Department of Immunology onstrated that TEC-mediated central tolerance could The Scripps Research Institute occur via recognition of antigen displayed by the TECs La Jolla, California 92037 themselves or after transfer of the antigens to BMderived, antigen-presenting cells (APCs) (Gallegos and Bevan, 2004).
Specific control of immunity by regulatory CD8 T cells
Cellular & molecular immunology, 2005
T lymphocytes with dedicated suppressor function (Treg) play a crucial role in the homeostatic control of immunity in the periphery. Several Treg phenotypes have now been identified in the CD4 and CD8 T cell populations, suggesting their down-regulatory function in both human and animal models of autoimmunity, transplantation and tumor immunity. Here we will focus on the CD8 Treg population and their ability to specifically inhibit a pathogenic autoimmune response. This review will detail the current advances in the knowledge of CD8 Treg in the context of antigen specificity, phenotype, MHC restriction, mechanism of action, and priming.
Immunology Letters, 2007
Expression of the CD8αα homodimer has been used to differentiate lymphoid (CD8α + ) from myeloid (CD8α − ) dendritic cells (DCs). We have reported that CD8α + and CD8α − DCs have differential abilities to stimulate proliferation in allogeneic T cells. However, no specific function has been attributed to DC-derived CD8α. The current study examines the hypothesis that CD8αα expression on DCs regulates DC-induced T cell activation. CD8α-transduced bone marrow-derived DCs were more potent stimulators of T cell proliferation, and produced significantly greater quantities of IL-12 in co-culture with T cells. LCK, a kinase whose expression is reported to be T cell-restricted and known to bind to the cytoplasmic tail of CD8αβ in T cells, was detected readily in primary CD8α + splenic DCs and at greater levels than CD8α − DCs from the same tissues. LCK also co-precipitated with CD8α on immunblots strongly suggesting its role in CD8α + DC-induced T cell activation. Collectively, these data show that CD8α expressed on DC may not only be a lineage/maturation marker but also contribute to DC function.