Development of a Th2 vaccine against autoimmune diseases using Interleukin-4

T helper type 1 (Th1) lymphocytes play a central role in the pathogenesis of Multiple Sclerosis (MS) and its animal model Experimental Autoimmune Encephalomyelitis (EAE). The cytokine Interleukin 4 (IL-4) inhibits the differentiation of T lymphocytes towards a Th1 phenotype and drives their differentiation into Th2 cells. In this project, we will establish and explore the potential of IL-4 - based vaccines as a new therapy for autoimmune diseases.

Protocols will be established that use IL-4 or IL-4 RNA to inducepr otective Th2 im-munity against antigens in the central nervous system (CNS) and to treat Experimen-tal Autoimmune Encephalomyelitis (EAE), the animal model of Multiple Sclerosis (MS).  The mechanisms of immunosuppression by IL-4 will be investigated using MHC class II tetramers to detect autoreactive T cells and fluorescently labelled anti-gens to directly investigate autoreactive B lymphocytes.

These newly developed tools will be used to assess in vivo activation, expansion and migration of autoreactive lymphocytes as well as their inactivation and elimination. We will further characterize immunological Th2-memory and assess whether IL-4 inhibits spreading of the immune reactivity towards secondary epitopes.  These in-vestigations are fundamental to our understanding of the mechanisms that underlie autoimmune diseases and a potential basis for the development of new strategies to treat autoimmune diseases such as Multiple Sclerossis.

These investigations are done in colaboration with
Dr. R. Weissert, Hertie Institute for Clinical Brain Research, Tübingen
Dr. S. Pascolo, Department of Immunology, Institute for Cell Biology, Tübingen
Dr. K. Ghoreschi, Department of Dermatology, University of Tübingen
Dr. M. Röcken, Department of Dermatology, University of Tübingen

Ansprechpartner: F. Bischof