Autoimmunity by non-Th1 cells

Minneapolis, MN -

Old school immunology divided responses into Th1 (inflammatory, intracellular responses) and Th2 (antibody mediated, extracellular responses). Classical autoimmune diseases such as Type 1 Diabetes, multiple sclerosis, and rheumatoid arthritis were considered primarily Th1 type diseases.

More recently, the "dogma" of Th1/Th2 immunity has been subjected to numerous critism. In a recent study (Wang et al. C57BL/6 Mice Genetically Deficient in IL-12/IL-23 and IFN-{gamma} Are Susceptible to Experimental Autoimmune Myasthenia Gravis, Suggesting a Pathogenic Role of Non-Th1 Cells. J Immunol. 2007 Jun 1;178(11):7072-80) the ability to induce autoimmunity in absence of Th1 responses is demonstrated.

The authors used a type of mouse model of myasthenia gravis in which immune response to the acetylcholine receptor is induced in B6 mice by immunization with the protein isolated from the Torpedo and admixed in Freund's adjuvant.

It was demonstrated that IL-12, IL-23 and IFN-gamma knockout mice, which lack Th1 cells, were capable of mounting an autoimmune attack in a similar fashion as the wildtype mice.

Interestingly CD4+ CD25+ Treg isolated from the knockout mice possessed weak suppressive activity in comparison to Treg from wildtype mice.

These data suggest that autoimmunity may occur in absence of a conventional Th1 response, and that some aspect of Th1 cytokines may be involved in Treg function.