Identification of T helper type 1-like, Foxp3+ regulatory T cells in human autoimmune disease.
ABSTRACT CD4(+)CD25(high)CD127(low/-) forkhead box p3 (Foxp3)(+) regulatory T cells (T(reg) cells) possess functional plasticity. Here we describe a higher frequency of T helper type 1 (T(H)1)-like, interferon-γ (IFN-γ)-secreting Foxp3(+) T cells in untreated subjects with relapsing remitting multiple sclerosis (RRMS) as compared to healthy control individuals. In subjects treated with IFN-β, the frequency of IFN-γ(+)Foxp3(+) T cells is similar to that in healthy control subjects. In vitro, human T(reg) cells from healthy subjects acquire a T(H)1-like phenotype when cultured in the presence of interleukin-12 (IL-12). T(H)1-like T(reg) cells show reduced suppressive activity in vitro, which can partially be reversed by IFN-γ-specific antibodies or by removal of IL-12.
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ABSTRACT: The cutaneous surface is exposed to a myriad of encounters with chemicals, allergens and microbes. Nevertheless, it withstands these environmental assaults without overt inflammation. We will discuss the role of T regulatory cells in a situation where this tissue homeostasis fails - cutaneous allergy, in particular contact hypersensitivity. Immune regulation is a complex process that is mediated by many cellular players. T regulatory cells have risen to particular prominence as potent immunosuppressors because their absence results in inflammation including skin allergy. Recent findings revealed that T regulatory cells comprise a heterogeneous group of subpopulations with specialized homing capabilities and suppressor functions. The stability of the T regulatory cell subset in proinflammatory microenvironments is controversially discussed. In addition, it has recently been shown that mechanisms by which T regulatory cells exert their immunosuppressive functions can be adopted by pathogenic effector T cells in certain situations. In cutaneous allergy, immunoregulatory mechanisms are dysfunctional. The cellular players comprise classical T regulatory cells as well as effector T cells with regulatory activities. Understanding their role in skin homeostasis and the mechanisms by which their regulatory functions are abrogated will yield novel therapeutic targets for the treatment of cutaneous allergies.Current Opinion in Allergy and Clinical Immunology 07/2012; 12(5):498-503. · 4.11 Impact Factor