Stat4-null non-obese diabetic mice: protection from diabetes and experimental allergic encephalomyelitis, but with concomitant epitope spread.

There is much interest in therapeutic manipulation of cytokine responses in autoimmunity, yet studies in mouse models have sometimes produced conflicting findings as to the role of particular mediators in disease. Examples include the contradictory findings regarding susceptibility to experimental allergic encephalomyelitis (EAE) or diabetes in knockout mice for various individual Th1 or Th2 cytokines or their receptors. An alternative approach to the analysis of Th1 and Th2 mechanisms in these diseases is to investigate strains carrying a null mutation for molecules involved in cytokine receptor signal transduction, signal transducer and activator of transcription (Stat4) and Stat6.

Spread of T lymphocyte immune responses to myelin epitopes with duration of multiple sclerosis.

Although the primary cause of multiple sclerosis (MS) is unclear, evidence supports a role for autoimmune attack of myelin by T lymphocytes. However, it has been difficult to relate patterns of autoimmunity to pathogenesis. In mouse models, the case has been made for relapsing and remitting disease driven by epitope spread: an initial lesion leads to presentation of central nervous system antigens, in turn triggering the next wave of autoimmune T cells of different specificity, the response thus broadening.