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Comparative Study
. 2003 May 1;170(9):4776-84.
doi: 10.4049/jimmunol.170.9.4776.

IFN-beta gene deletion leads to augmented and chronic demyelinating experimental autoimmune encephalomyelitis

Ingrid Teige  1 , Alexandra Treschow, Anna Teige, Ragnar Mattsson, Vaidrius Navikas, Tomas Leanderson, Rikard Holmdahl, Shohreh Issazadeh-Navikas
Affiliations
Comparative Study

IFN-beta gene deletion leads to augmented and chronic demyelinating experimental autoimmune encephalomyelitis

Ingrid Teige et al. J Immunol. .

Abstract

Since the basic mechanisms behind the beneficial effects of IFN-beta in multiple sclerosis (MS) patients are still obscure, here we have investigated the effects of IFN-beta gene disruption on the commonly used animal model for MS, experimental autoimmune encephalomyelitis (EAE). We show that IFN-beta knockout (KO) mice are more susceptible to EAE than their wild-type (wt) littermates; they develop more severe and chronic neurological symptoms with more extensive CNS inflammation and demyelination. However, there was no discrepancy observed between wt and KO mice regarding the capacity of T cells to proliferate or produce IFN-gamma in response to recall Ag. Consequently, we addressed the effect of IFN-beta on encephalitogenic T cell development and the disease initiation phase by passive transfer of autoreactive T cells from KO or wt littermates to both groups of mice. Interestingly, IFN-beta KO mice acquired a higher incidence and augmented EAE regardless of the source of T cells. This shows that the anti-inflammatory effect of endogenous IFN-beta is predominantly exerted on the effector phase of the disease. Histopathological investigations of CNS in the effector phase revealed an extensive microglia activation and TNF-alpha production in IFN-beta KO mice; this was virtually absent in wt littermates. This coincided with an increase in effector functions of T cells in IFN-beta KO mice, as measured by IFN-gamma and IL-4 production. We suggest that lack of endogenous IFN-beta in CNS leads to augmented microglia activation, resulting in a sustained inflammation, cytokine production, and tissue damage with consequent chronic neurological deficits.

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