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.
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Maria
M
Bettini
Dario A A
DA
Vignali
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