MYELIN BASIC PROTEIN-SPECIFIC T-HELPER-2 (TH2) CELLS CAUSE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN IMMUNODEFICIENT HOSTS RATHER THAN PROTECT THEM FROM THE DISEASE

Chronic inflammatory autoimmune diseases such as multiple sclerosis, d iabetes, and rheumatoid arthritis are caused by CD4(+) Th1 cells. Beca use Th2 cells antagonize Th1 cell functions in several ways, it is bel ieved that immune deviation towards Th2 can prevent or curl autoimmune diseases. Experimental autoimmune encephalomyelitis (EAE) is a demyel inating disease used as a model for multiple sclerosis. Using an adopt ive transfer system we assessed the role of Th1 and Th2 cells in EAE. In vitro generated Th1 and Th2 cells from myelin basic protein (MBP)-s pecific TCR transgenic mice were transferred into normal and immunodef icient mice. Th1 cells caused EAE in all recipients after a brief prec linical phase. Surprisingly, Th2 cells also caused EAE in RAG-1 KO mic e and in alpha beta T cell-deficient mice, albeit after a longer precl inical phase. Normal or gamma delta T cell-deficient mice were resista nt to EAE induced by Th2 cells. The histopathological features of this disease resembled those of an allergic process. In addition, disease induction by Th1 cells was not altered by coadministration of Th2 cell s in any of the recipients. These findings indicate that MBP-specific Th2 cells have the potential to induce EAE and that the disease induce d by previously activated Th1 cells cannot be prevented by normal lymp hocytes nor by previously activated Th2 cells.