The CD4-Thl model for multiple sclerosis: a crucial re-appraisal

Multiple sclerosis (MS), an acquired spontaneous chronic inflammatory demyelinating disease of the human central nervous system [CNS) has features of autoimmunity to myelin, directed by CD4(+) J cells, which are polarized to production of type I cytokines. similarities between MS and models of Th1-driven brain inflammation led to assumptions that the two are equivalent and that models can be used to decipher MS and predict responses to therapy. However, over decades, numerous bits of data incompatible with a simple CD4-Th1 hypothesis have accumulated. They suggest that besides Th1 cells, other immunological mechanisms and a neurodegenerative component within the target tissue might contribute to the initiation, propagation and modification of this disease. Taken together, these issues prompt reconsideration of the use of pure CD4-Th1 models in favor of a view that MS is likely to be heterogeneous and might not be strictly autoimmune.