Regulation of self-tolerance by Qa-1-restricted CD8(+) regulatory T cells

Harvard University, Cambridge, Massachusetts, United States
Seminars in Immunology (Impact Factor: 5.17). 12/2011; 23(6):446-52. DOI: 10.1016/j.smim.2011.06.001
Source: PubMed


Mounting an efficient immune response to pathogens while avoiding damage to host tissues is the central task of the immune system. Emerging evidence has highlighted the contribution of the CD8(+) lineage of regulatory T cells to the maintenance of self-tolerance. Specific recognition of the MHC class Ib molecule Qa-1 complexed to peptides expressed by activated CD4(+) T cells by regulatory CD8(+) T cells triggers an inhibitory interaction that prevents autoimmune responses. Conversely, defective Qa-1-restricted CD8(+) regulatory activity can result in development of systemic autoimmune disease. Here, we review recent research into the cellular and molecular basis of these regulatory T cells, their mechanism of suppressive activity and the potential application of these insights into new treatments for autoimmune disease and cancer.

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    • "In animal models, early studies found that polyclonal CD8 T cells can limit disease severity and relapses of CD4 T cell-mediated EAE (Jiang et al., 1992; Koh et al., 1992). The ability of CD8 T cells to regulate CNS autoimmune disease may occur by CD8 T cells targeting activated CD4 T cells through the recognition of peptide displayed on MHC class I and Ib molecules, as well as by secreting IL-10 and other anti-inflammatory soluble mediators (Jiang and Chess, 2006; Goverman, 2009; Kim and Cantor, 2011; Ortega et al., 2013). Thus, different subsets of CD8 T cells, like their CD4 counterparts, likely play pathogenic and immuno-regulatory roles in MS (Huseby et al., 2012). "
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    ABSTRACT: Multiple Sclerosis (MS) is an inflammatory disease of the Central Nervous System (CNS) that causes the demyelination of nerve cells and destroys oligodendrocytes, neurons and axons. Historically, MS has been thought of as a T cell-mediated autoimmune disease of CNS white matter. However, recent studies have identified gray matter lesions in MS patients, suggesting that CNS antigens other than myelin proteins may be involved during the MS disease process. We have recently found that T cells targeting astrocyte-specific antigens can drive unique aspects of inflammatory CNS autoimmunity, including the targeting of gray matter and white matter of the brain and inducing heterogeneous clinical disease courses. In addition to being a target of T cells, astrocytes play a critical role in propagating the inflammatory response within the CNS induced NF-κB signaling. Here, we will discuss the pathophysiology of CNS inflammation mediated by T cell-glial cell interactions and its contributions to CNS autoimmunity.
    Full-text · Article · Aug 2015 · Frontiers in Cellular Neuroscience
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    • "T cells, a subpopulation of adaptive lymphocytes, play an important role in immunity to intracellular pathogens and tumors (Gattinoni et al. 2012; Klenerman and Hill 2005; Kuang et al. 2010; Lu et al. 2014). They also contribute to the regulation of pathologic processes such as autoimmune and allergic disorders (Huber et al. 2009; Kim and Cantor 2011; Loser et al. 2010; Tang et al. 2012; Visekruna et al. 2013). Naı¨ve CD8 ? "
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    ABSTRACT: It is well established that CD8(+) T cells constitute an important branch of adaptive immunity contributing to clearance of intracellular pathogens and providing long-term protection. These functions are mostly fulfilled by the best characterized subpopulation of CD8(+) T cells, the cytotoxic T lymphocytes (also called Tc1 cells), owing to their ability to kill infected cells and to secrete cytokines such as interferon-γ and tumor necrosis factor-α. However, there is growing evidence for alternative CD8(+) T cell fates influencing CD4(+) T-cell-mediated responses in the context of allergy, autoimmunity and infections. Thus, like subpopulations of CD4(+) T cells, also CD8(+) T cells under particular conditions acquire the expression of interleukin (IL)-4, IL-5, IL-9, IL-13, IL-17 or suppressive activity and thereby influence immune responses. The process of CD8(+) T-cell differentiation is dictated by antigen strength, co-stimulatory molecules and cytokines. These environmental cues induce transcription factors further specifying CD8(+) T-cell decision into Tc1, Tc2, Tc9, Tc17 or CD8(+) T regulatory fate. Here, we discuss our current understanding about functional diversity of effector CD8(+) T cells and contribution of transcription factors to this process.
    Full-text · Article · May 2014 · Archivum Immunologiae et Therapiae Experimentalis

  • No preview · Article · Dec 2011 · Seminars in Immunology
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