Regulatory T cells and inhibitory cytokines in autoimmunity

Abstract

Regulatory T cells and inhibitory cytokines in autoimmunity Maria Bettini and Dario A. A. Vignali Department of Immunology, St. Jude Children’s Research Hospital, Memphis TN 38105, USA Summary of recent advances Foxp3+ regulatory T cells (Tregs) contribute significantly to the maintenance of peripheral tolerance, but they ultimately fail in autoimmune diseases. The events that lead to Treg failure in controlling autoreactive effector T cells (Teffs) during autoimmunity are not completely understood. In this review, we discuss possible mechanisms for this subversion as they relate to type 1 diabetes (T1D) and multiple sclerosis (MS). Recent studies emphasize (i) the role of inflammatory cytokines, such as IL-6, in inhibiting or subverting Treg function, (ii) the issue of Treg plasticity, (iii) the possible resistance of autoimmune T cells to Treg-mediated control, and (iv) Treg-associated inhibitory cytokines TGFβ, IL-10 and IL-35 in facilitating Treg suppressive activity and promoting Treg generation. These recent advances place a large emphasis on the local tissue specific inflammatory environment as it relates to Treg function and disease development. Introduction Autoimmunity ensues when central and/or peripheral tolerance barriers are overcome, thereby allowing the activation of self-reactive T cells, which induce tissue destruction. Most self- reactive T cells are deleted in the thymus, a process referred to as central tolerance. The few remaining self-reactive T cells that enter the periphery are controlled by peripheral tolerance mechanisms, in which Foxp3+ Tregs have emerged as the primary mediators [1]. Autoimmune disease develops when this last tolerance barrier is compromised. It has been shown that many individuals with no autoimmune manifestations harbor self-reactive T cells [2]. Thus, the continual battle between self-reactive T cells and suppressive Tregs is critical in determining whether autoimmunity commences. Many autoimmune diseases manifest the

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