Foxp3(+) regulatory T (T(reg) ) cells are essential for maintaining self-tolerance and preventing autoimmune reactions. T(reg) cells arise as a consequence of self-antigen recognition during the maturation of cells in the thymus, and also following self-antigen recognition in the periphery. Both thymic and peripherally generated T(reg) cells respond to antigen recognition by expanding in number, increasing their suppressive activity, and accumulating in the tissue where the antigen is located. A fraction of these activated "effector" T(reg) cells survive even in the absence of antigen expression and continue to control inflammatory reaction in the tissues, thus functioning as a population of "memory" T(reg) cells. Antigen exposure and the presence of IL-2 are key determinants in the generation of memory T(reg) cells. These results provide a foundation for studying the role of memory T(reg) cells in controlling and treating autoimmune disorders and for testing the hypothesis that defects in the generation and maintenance of these cells underlie chronic, relapsing inflammatory diseases.
"The field of regulatory T cells, although relatively recent, has had an explosion of knowledge driven by detailed experimental work (20, 65, 72, 123, 124). Indeed there are many more studies than we could possibly review or even allude to in this mini-review. "
[Show abstract][Hide abstract] ABSTRACT: To maintain immunological balance the organism has to be tolerant to self while remaining competent to mount an effective immune response against third-party antigens. An important mechanism of this immune regulation involves the action of regulatory T-cell (Tregs). In this mini-review, we discuss some of the known and proposed mechanisms by which Tregs exert their influence in the context of immune regulation, and the contribution of mathematical modeling for these mechanistic studies. These models explore the mechanisms of action of regulatory T cells, and include hypotheses of multiple signals, delivered through simultaneous antigen-presenting cell (APC) conjugation; interaction of feedback loops between APC, Tregs, and effector cells; or production of specific cytokines that act on effector cells. As the field matures, and competing models are winnowed out, it is likely that we will be able to quantify how tolerance-inducing strategies, such as CD4-blockade, affect T-cell dynamics and what mechanisms explain the observed behavior of T-cell based tolerance.
Frontiers in Immunology 11/2013; 4:378. DOI:10.3389/fimmu.2013.00378
"Treg are effective suppressors of pathogenic effector T cells of T helper 17 (Th17) and Th1 lineage, both of which have been invoked in the pathogenesis of autoimmune arthritis in different experimental models as well as patients with RA. Natural Treg constitutively express CD25 and Forkhead box p3 (Foxp3), whereas induced Treg express it along with induction of Foxp3 expression when they develop from CD4+CD25− T cells under appropriate conditions of T-cell activation [23–26]. The above-mentioned HLXL-induced changes also represent the likely mechanisms by which HLXL exerts its antiarthritic effect in rats with AA. "
[Show abstract][Hide abstract] ABSTRACT: Rheumatoid arthritis (RA) is a chronic inflammatory disease of autoimmune origin. Huo-luo-xiao-ling dan (HLXL) is an herbal mixture that has been used in traditional Chinese medicine over several decades to treat chronic inflammatory diseases including RA. However, the mechanism of the anti-arthritic action of this herbal remedy is poorly understood at the molecular level. In this study, we determined by microarray analysis the effects of HLXL on the global gene expression profile of the draining lymph node cells (LNC) in the rat adjuvant arthritis (AA) model of human RA. In LNC restimulated in vitro with the disease-related antigen mycobacterial heat-shock protein 65 (Bhsp65), 84 differentially expressed genes (DEG) (64 upregulated and 20 downregulated) versus 120 DEG (94 upregulated and 26 downregulated) were identified in HLXL-treated versus vehicle (Water)-treated rats, respectively, and 62 DEG (45 upregulated and 17 downregulated) were shared between the two groups. The most affected pathways in response to HLXL treatment included immune response, inflammation, cellular proliferation and apoptosis, and metabolic processes, many of which are directly relevant to arthritis pathogenesis. These results would advance our understanding of the mechanisms underlying the anti-arthritic activity of HLXL.
Evidence-based Complementary and Alternative Medicine 07/2013; 2013:524746. DOI:10.1155/2013/524746 · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In addition to their stem/progenitor properties, mesenchymal stromal cells (MSCs) possess broad immunoregulatory properties that are being investigated for potential clinical application in treating immune-based disorders. An informed view of the scope of this clinical potential will require a clear understanding of the dynamic interplay between MSCs and the innate and adaptive immune systems. In this Review, we outline current insights into the ways in which MSCs sense and control inflammation, highlighting the central role of macrophage polarization. We also draw attention to functional differences seen between vivo and in vitro contexts and between species. Finally, we discuss progress toward clinical application of MSCs, focusing on GvHD as a case study.
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