[Show abstract][Hide abstract] ABSTRACT: CD4⁺CD25⁺Foxp3⁺ T lymphocytes, known as regulatory T cells or T(regs), have been proposed to be a lineage of professional immune suppressive cells that exclusively counteract the effects of the immunoprotective "helper" and "cytotoxic" lineages of T lymphocytes. Here we discuss new concepts on the mechanisms and functions of T(regs). There are several key points we emphasize: 1. Tregs exert suppressive effects both directly on effector T cells and indirectly through antigen-presenting cells; 2. Regulation can occur through a novel mechanism of cytokine consumption to regulate as opposed to the usual mechanism of cytokine/chemokine production; 3. In cases where CD4⁺ effector T cells are directly inhibited by T(regs), it is chiefly through a mechanism of lymphokine withdrawal apoptosis leading to polyclonal deletion; and 4. Contrary to the current view, we discuss new evidence that T(regs), similar to other T-cells lineages, can promote protective immune responses in certain infectious contexts (Chen et al., 2011; Pandiyan et al., 2011). Although these points are at variance to varying degrees with the standard model of T(reg) behavior, we will recount developing findings that support these new concepts.
Frontiers in Immunology 11/2011; 2:60. DOI:10.3389/fimmu.2011.00060
[Show abstract][Hide abstract] ABSTRACT: Asthma is a chronic inflammatory airway disease involving complex interplay between resident and infiltrative cells, which in turn are regulated by a wide range of host mediators. Identifying useful biomarkers correlating with clinical symptoms and degree of airway obstruction remain important to effective future asthma treatments. Transforming growth factor β (TGF-β) is a major mediator involved in pro-inflammatory responses and fibrotic tissue remodelling within the asthmatic lung. Its role however, as a therapeutic target remains controversial. The aim of this review is to highlight its role in severe asthma including interactions with adaptive T-helper cells, cytokines and differentiation through regulatory T-cells. Associations between TGF-β and eosinophils will be addressed and the effects of genetic polymorphisms of the TGF-β1 gene explored in the context of asthma. We highlight TGF- β1 as a potential future therapeutic target in severe asthma including its importance in identifying emerging clinical phenotypes in asthmatic subjects who may be suitable for individualised therapy through TGF-β modulation.
Respiratory Medicine 09/2014; 108(10). DOI:10.1016/j.rmed.2014.08.008 · 2.92 Impact Factor
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