Strain difference in susceptibility to experimental autoimmune encephalomyelitis between Albino Oxford and Dark Agouti rats correlates with disparity in production of IL-17, but not nitric oxide

Abstract

Albino Oxford (AO) rats, unlike Dark Agouti (DA) rats are resistant to the induction of experimental autoimmune encephalomyelitis (EAE). The reason for the resistance could be some restraining mechanism preventing auto-aggressive cell activation at the level of draining lymph nodes (DLN) during the induction phase of the disease. Such a mechanism could be anti-proliferative action of nitric oxide (NO), which has already been shown of importance for the resistance of several rat strains to the induction of the disease. Importantly, number of AO DLN cells (DLNC) is markedly lower and with lower proliferative response to myelin basic protein (MBP) ex vivo in comparison to DA DLNC in the inductive phase of EAE, thus implying that in AO rats DLNC do not proliferate as extensively as in DA rats. We show that AO rats do not produce larger quantities of NO than DA rats after immunization. Further, DLNC of immunized AO rats have significantly lower mRNA expression and synthesis of interferon (IFN)-gamma and interleukin (IL)-17 compared to DLNC of DA rats. Collectively, these results suggest that there is a substantial difference between EAE-resistant AO rats and EAE-prone DA rats in the initiation of autoimmune response. This difference seems to be independent of anti-proliferative actions of NO, but correlates with impaired IL-17 production in AO rats.