Carbone, Fortunata (2011) Regulatory T cell proliferative potential as novel marker to investigate immune tolerance and clinical progression in Multiple Sclerosis. [Tesi di dottorato] (Inedito)

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Abstract

In autoimmune disorders such as Multiple Sclerosis (MS) one of the determining alteration is the breakdown of self-antigen immune-tolerance. Peripheral immune tolerance is maintained, at least in part, by Regulatory T cells (Treg). Several studies have shown that either defects in the frequency or the suppressive capacity of Treg cells can contribute to the development of break of self-tolerance, and that in animal models of autoimmunity, adoptive transfer of Treg cells was able to stop disease process. Treg cells are known to be anergic in vitro to T cell receptor-induced (TCR) stimulation and this state correlates with their in vitro suppressive capacity. It has been reported that there are differences in the number of Treg cells in MS patients when compared with healthy controls. However there is also extensive evidence indicating a defect in the suppressive function of Treg cells from MS patients. In previous studies we showed that Treg cells produce an higher amount of leptin when compared with effector T cells and that leptin acts as a negative signal for the proliferation of Treg cells. In vitro leptin neutralization results in Treg cells proliferation. Although in last few years several studies have been performed to understand the molecular mechanism leading to autoimmune disorders development, there are no surrogate markers to predict the clinical progression of autoimmune diseases and the clinical response to the classical therapeutic regimes.

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