From Vanilla to 28 Flavors: Multiple Varieties of T Regulatory Cells

Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Immunity (Impact Factor: 21.56). 09/2006; 25(2):195-201. DOI: 10.1016/j.immuni.2006.08.003
Source: PubMed


Numerous T cell subpopulations have now been claimed to exhibit regulatory activity. Shevach discusses the current understanding of the different subsets of T regulatory cells and provides a perspective on the current areas of uncertainly and controversy in the field.

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    • "Interleukin-10 (IL-10) and transforming growth factor-í µí»½ (TGF-í µí»½) were hypothesized to be involved in Treg mediated immunosuppression since Tregs could secrete these cytokines and these cytokines are irrefutably immunosuppressive, yet their contribution to the function of thymus-derived, naturally occurring Tregs is still a matter of debate [40]. In order to achieve the maximal regulatory activity of Tregs, IL-10 and TGF-í µí»½ were critically required in vivo, yet meanwhile studies showed that neutralization of either IL-10 or TGF-í µí»½ did not abrogate in vitro suppression [41] [42]; therefore, this hypothesis still requires more evidence to refine. "
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    ABSTRACT: The underlying mechanism of ischemic stroke is not completely known. Regulatory T cells (Tregs), a subset of T cells, play a pivotal role in the pathophysiological process of ischemic stroke. However, there is also controversy over the role of Tregs in stroke. Hence, the function of Tregs in ischemic stroke has triggered a heated discussion recently. In this paper, we reviewed the current lines of evidence to describe the full view of Tregs in stroke. We would like to introduce the basic concepts of Tregs and then discuss their paradox function in ischemic stroke. On one side, Tregs could protect brain against ischemic injury via modulating the inflammation process. On the other side, they exaggerated the insult by causing microvascular dysfunction. They also interfered with the neurological function recovery. In addition, the reasons for this paradox role would be discussed in the review and the prospective of the clinical application of Tregs was also included. In conclusion, Tregs contributed to the outcome of ischemic stroke, while more lines of evidence are needed to understand how Tregs regulate the immune system and influence the outcome of stroke.
    The Scientific World Journal 10/2013; 2013(7):174373. DOI:10.1155/2013/174373 · 1.73 Impact Factor
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    • "The phenotypic findings argue against an intraepithelial lymphocyte origin or derivation from natural or induced regulatory T-cells (Tregs). [25], [26] It is known that epigenetic regulation of the FoxP3 gene, as well as post-translational modifications of the FoxP3 protein, modulate cellular FoxP3 levels and stability and hence Treg differentiation and function. [27] Recent studies have shown that acetylation of FoxP3 by the histone acetyltransferase p300 prevents polyubiquitination and its proteasomal degradation leading to increase protein stability and increased Treg suppressive capacity, while deacetylation by Sirtuin 1 (Sirt1), an NAD(+) dependant class III histone/protein deacetylase, leads to diminution or loss of FoxP3 protein and inhibition of Treg function. "
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    ABSTRACT: Enteropathy-associated T-cell lymphomas (EATL) are rare and generally aggressive types of peripheral T-cell lymphomas. Rare cases of primary, small intestinal CD4+ T-cell lymphomas with indolent behavior have been described, but are not well characterized. We describe morphologic, phenotypic, genomic and clinical features of 3 cases of indolent primary small intestinal CD4+ T-cell lymphomas. All patients presented with diarrhea and weight loss and were diagnosed with celiac disease refractory to a gluten free diet at referring institutions. Small intestinal biopsies showed crypt hyperplasia, villous atrophy and a dense lamina propria infiltrate of small-sized CD4+ T-cells often with CD7 downregulation or loss. Gastric and colonic involvement was also detected (n = 2 each). Persistent, clonal TCRβ gene rearrangement products were detected at multiple sites. SNP array analysis showed relative genomic stability, early in disease course, and non-recurrent genetic abnormalities, but complex changes were seen at disease transformation (n = 1). Two patients are alive with persistent disease (4.6 and 2.5 years post-diagnosis), despite immunomodulatory therapy; one died due to bowel perforation related to large cell transformation 11 years post-diagnosis. Unique pathobiologic features warrant designation of indolent small intestinal CD4+ T-cell lymphoma as a distinct entity, greater awareness of which would avoid misdiagnosis as EATL or an inflammatory disorder, especially celiac disease.
    PLoS ONE 07/2013; 8(7):e68343. DOI:10.1371/journal.pone.0068343 · 3.23 Impact Factor
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    • "''Tolerogenic DCs'' can prime Th cells to become regulatory T cells. Among these, Tr1 cells are characterized by the production of low amounts of IFN-g but high levels of IL-10 (Groux et al., 1997; O'Garra and Vieira, 2004; Shevach, 2006). Moreover, it has been reported that immune modulation by Tr1 cells reduces antigen-specific IgE but not antigen-specific IgG1 and IgG2a levels, which is similar to our findings following exposure to Vf (Cottrez et al., 2000), but in contrast to, e.g., low-zone tolerance that has been reported to tremendously reduce specific immunoglobulin levels (Steinbrink et al., 1996). "
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    ABSTRACT: Beneficial effects of non-pathogenic bacteria are increasingly recognized. We reported in a placebo-controlled study with atopic dermatitis (AD) patients that cutaneous exposure to lysates of non-pathogenic bacteria alleviates skin inflammation. To now unravel underlying mechanisms, immune consequences of sensing non-pathogenic bacterium Vitreoscilla filiformis lysate (Vf) were characterized analyzing (i) differentiation of dendritic cells (DC) and, consecutively, (ii) effector functions of DC and Th cells in vitro and in a murine model of AD in NC/Nga mice in vivo. Topical treatment with Vf significantly reduced AD-like inflammation in NC/Nga mice. Importantly, cutaneous exposure to Vf in combination with the allergen FITC significantly reduced also subsequent allergen-induced dermatitis indicating active immune modulation. Indeed, innate sensing of Vf predominantly induced IL-10 producing DC, which was dependent on TLR2-activation. Vf-induced IL-10+ DC primed naïve CD4+ T helper cells to become regulatory IFN-γ(low) IL-10(high) Tr1 cells. These IL-10(high) Tr1 cells were also induced by Vf in vivo and strongly suppressed T effector cells and inflammation. In conclusion we show that innate sensing of non-pathogenic bacteria by TLR2 induces tolerogenic DC and regulatory Tr1 cells suppressing T effector cells and cutaneous inflammation. These findings indicate a promising therapeutic strategy for inflammatory skin diseases like AD.Journal of Investigative Dermatology accepted article preview online, 28 June 2013; doi:10.1038/jid.2013.291.
    Journal of Investigative Dermatology 06/2013; DOI:10.1038/jid.2013.291 · 7.22 Impact Factor
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