Essential role of TGF-beta in the natural resistance to experimental allergic encephalomyelitis in rats

Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmu ne disease induced in susceptible rat strains by a single immunization with myelin basic protein (MBP). The Lewis (LEW) strain is susceptible to disea se induction while the Brown Norway (BN) strain is resistant. This resistan ce involves non-MHC genes since congenic BN-l L rats, with LEW MHC on a BN- derived background, are also resistant. In the present study we show that, upon immunization with MBP, the non-MHC-encoded resistance to develop clini cal EAE in BN-1L rats is associated with a decreased production of IFN-gamm a. This may be due to a difference between LEW and BN-IL rats in their abil ity to produce regulatory cytokines such as IL-4, IL-10 and TGF-beta. In co mparison to LEW rats, immune lymph node cells from BN-I L rats express an i ncreased amount of IL-4 mRNA but produce less IL-10. Furthermore, the sera from BN-1L rats contain higher amounts of active TGF-beta1. Therefore, we h ave investigated the involvement of IL-4 and TGF-beta in the resistance of BN-1L rats to develop EAE using neutralizing mAb. Neutralization of TGF-bet a, but not IL-4, renders BN-1L rats susceptible to clinical EAE without aff ecting the proliferation or the cytokine repertoire of immune lymph node ce lls. With respect to the origin of the endogenous TGF-beta production, we e xcluded the involvement of CD8 T cells and discuss a possible role of plate lets and of CD4 T cells exhibiting the CD45RC(low) phenotype.