Figure 2.

A four-step model for MHC class II-associated autoimmune diseases. Certain class II MHC-associated autoimmune diseases arise through a series of four steps: (1) T cell activation regardless of antigen specificity; (2) local events inducing a tissue-specific accumulation of activated T cells; (3) transient activation of the IL-6 amplifier, which is triggered by CD4+ T cell-derived cytokines such as IL-17A; and (4) enhanced sensitivity to T cell-derived cytokines and/or IL-6 in type 1 collagen+ cells in the target tissue. Following these four steps, chronic activation of the IL-6 amplifier followed by the development of an autoimmune disease occurs. It is likely that each step interacts with the others, and the degree of the contribution of each to the pathogenesis varies with the disease.