Toll-like receptors: paving the path to T cell-driven autoimmunity?

The development of autoimmunity is often associated with the presence of pathogen-associated molecular patterns (PAMPs) and signaling through toll-like receptors (TLRs). Largely, the importance of PAMP–TLR ligation has been attributed to inducing the maturation of antigen-presenting cells and production of proinflammatory cytokines and chemokines. Recent evidence now shows that PAMPs can activate effector and regulatory T cells revealing a further level of complexity in the development of autoimmunity. TLR signaling on T cells acts as a form of costimulation, lowering the ‘strength of signal’ required for proliferation and survival. This apparent mechanism of immune homeostasis may break tolerance or anergy upon pathogen infection and promote the development of immune responses against self-antigens.