Regulatory T-cell compartmentalization and trafficking

Department of Surgery, University of Michigan, Ann Arbor, USA.
Blood (Impact Factor: 10.45). 08/2006; 108(2):426-31. DOI: 10.1182/blood-2006-01-0177
Source: PubMed


CD4(+)CD25(+)FOXP3(+) regulatory T cells (CD4(+) Treg cells) are thought to differentiate in the thymus and immigrate from the thymus to the periphery. Treg cells can regulate both acquired and innate immunity through multiple modes of suppression. The cross-talk between Treg cells and targeted cells, such as antigen-presenting cells (APCs) and T cells, is crucial for ensuring suppression by Treg cells in the appropriate microenvironment. Emerging evidence suggests that Treg compartmentalization and trafficking may be tissue or/and organ specific and that distinct chemokine receptor and integrin expression may contribute to selective retention and trafficking of Treg cells at sites where regulation is required. In this review, the cellular and molecular signals that control specialized migration and retention of Treg cells are discussed.

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Available from: Ilona Kryczek, Jan 28, 2016
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    • "In rheumatoid arthritis, abnormal Treg function may stem from defective CTLA-4 (139); therefore, augmentation of functional CTLA-4+ Tregs may be advantageous in rheumatoid arthritis. Understanding Treg subset trafficking and survival via chemokine and integrin signals will be key to selecting appropriate Treg subsets for a given application (140). "
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    ABSTRACT: Regulatory T cells (Tregs) suppress exuberant immune system activation and promote immunologic tolerance. Because Tregs modulate both innate and adaptive immunity, the biomedical community has developed an intense interest in using Tregs for immunotherapy. Conditions that require clinical tolerance to improve outcomes - autoimmune disease, solid organ transplantation, and hematopoietic stem cell transplantation - may benefit from Treg immunotherapy. Investigators have designed ex vivo strategies to isolate, preserve, expand, and infuse Tregs. Protocols to manipulate Treg populations in vivo have also been considered. Barriers to clinically feasible Treg immunotherapy include Treg stability, off-cell effects, and demonstration of cell preparation purity and potency. Clinical trials involving Treg adoptive transfer to treat graft versus host disease preliminarily demonstrated the safety and efficacy of Treg immunotherapy in humans. Future work will need to confirm the safety of Treg immunotherapy and establish the efficacy of specific Treg subsets for the treatment of immune-mediated disease.
    Full-text · Article · Feb 2014 · Frontiers in Immunology
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    • "For instance, we may increase the number of FoxP3+CD25+CD4+ Tregs in the poststroke brain by adoptive transfer via intravenous injection, stimulation by pharmacological compounds, such as retinal and albumin, and genetic engineering techniques [32, 64, 93–95]. Since appropriate Treg migration and retention are required for Treg-mediated immune suppression, which can be modulated [96], we also hypothesize that increase of FoxP3+CD25+CD4+ Treg mobilization into CNS would be beneficial. Nevertheless, a series of critical issues associated with FoxP3+CD25+CD4+ Tregs remain to be resolved. "
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    ABSTRACT: Stroke is a common, debilitating trauma that has an incompletely elucidated pathophysiology and lacks an effective therapy. FoxP3(+)CD25(+)CD4(+) regulatory T cells (Tregs) suppress a variety of normal physiological and pathological immune responses via several pathways, such as inhibitory cytokine secretion, direct cytolysis induction, and antigen-presenting cell functional modulation. FoxP3(+)CD25(+)CD4(+) Tregs are involved in a variety of central nervous system diseases and injuries, including axonal injury, neurodegenerative diseases, and stroke. Specifically, FoxP3(+)CD25(+)CD4(+) Tregs exert neuroprotective effects in acute experimental stroke models. These beneficial effects, however, are difficult to elucidate. In this review, we summarized evidence of FoxP3(+)CD25(+)CD4(+) Tregs as potentially important immunomodulators in stroke pathogenesis and highlight further investigations for possible immunotherapeutic strategies by modulating the quantity and/or functional effects of FoxP3(+)CD25(+)CD4(+) Tregs in stroke patients.
    Full-text · Article · Aug 2013 · Clinical and Developmental Immunology
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    • "Further studies show that Tregs infiltrate and move into inflammatory sites in various inflammatory diseases and suppress effector T-cell function. Tregs, consistent with their central role in the preservation of tissue integrity, can accumulate at inflammation or infection sites [31, 32]. Indeed, there is agreement among many investigators of various diseases that there is increased recruitment of CD4+CD25high Tregs at inflammatory sites [33–37]. "
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