Regulatory T cells and inhibitory cytokines in autoimmunity.
Foxp3(+) regulatory T cells (T(regs)) contribute significantly to the maintenance of peripheral tolerance, but they ultimately fail in autoimmune diseases. The events that lead to T(reg) failure in controlling autoreactive effector T cells (T(effs)) 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 firstly, the role of inflammatory cytokines, such as IL-6, in inhibiting or subverting T(reg) function; secondly, the issue of T(reg) plasticity; thirdly, the possible resistance of autoimmune T cells to T(reg)-mediated control; and fourthly, T(reg)-associated inhibitory cytokines TGFbeta, IL-10 and IL-35 in facilitating T(reg) suppressive activity and promoting T(reg) generation. These recent advances place a large emphasis on the local tissue specific inflammatory environment as it relates to T(reg) function and disease development.
Bettini
Maria
M
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Vignali
Dario A A
DA
D000818:Animals; D015551:Autoimmunity; D016207:Cytokines / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D006801:Humans; D009103:Multiple Sclerosis / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
D016207:Cytokines