ABSTRACT
In the development of T-cell-mediated autoimmune disease, inflammatory mediators are essential and they play roles that are essentially the same as in all other immune-mediated processes. Apart from providing signals that trigger innate (and usually local) antimicrobial responses, they are also crucial to set the scene for autoreactive T lymphocytes to become activated. To appreciate this latter aspect, it is important to understand how inflammatory mediators influence the activation of T cells in general. The activation of T cells requires clustering of a wide range of highly specialized molecules on the surface as well as on the inside of a T cell to form a supramolecular complex for productive interaction with antigen-presenting cells (APC) (1,2). Short molecules form the center of this supramolecular complex, and include the T-cell receptor (TCR)–CD3 complex and, for example, protein kinase C. Longer molecules such as integrins and CD45 are positioned on the outer rim of the complex. At the same time, surface rafts are formed that functionally link molecules of the TCR complex with intracellular signaling molecules, allowing interactions at the surface of the T cell to be translated into intracellular activation signals that regulate gene expression.
