Priming of myelin-specific T cells in the absence of dendritic cells results in accelerated development of Experimental Autoimmune Encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is an established animal model of multiple sclerosis (MS). Inflammatory CD4(+) T cell responses directed against CNS antigens, including myelin proteolipid protein (PLP), are key mediators of EAE. Dendritic cells (DCs) are critical for the induction of T cell responses against infectious agents. However, the importance of DCs in priming self-reactive CD4(+) T cells in autoimmune disease such as MS has been unclear. To determine the requirement of DCs in PLP-specific CD4(+) T cell responses and EAE, we genetically deleted CD11c(+) DCs in PLP T cell receptor (TCR) transgenic SJL mice constitutively. DC deficiency did not impair the development, selection or the pathogenic function of PLP-specific CD4(+) T cells in these mice, and resulted in accelerated spontaneous EAE compared to DC sufficient controls. In addition, using a genetic approach to ablate DCs conditionally in SJL mice, we show that CD11c(+) DCs were dispensable for presenting exogenous or endogenous myelin antigen to PLP-specific T cells and for promoting pro-inflammatory T cell responses and severe EAE. Our findings demonstrate that constitutive or conditional ablation of CD11c(+) DCs diminished self-tolerance to PLP autoantigen. They further show that in the absence of DCs, non-DCs can efficiently present CNS myelin antigens such as PLP to self-reactive T cells, resulting in accelerated onset of spontaneous or induced EAE.

Automated summary

This study investigated the role of dendritic cells (DCs) in the development of autoimmune disease, particularly in relation to self-reactive CD4(+) T cells in multiple sclerosis (MS). The findings indicate that DC deficiency can reduce immune tolerance to self-antigens, such as PLP, leading to accelerated onset of EAE. Additionally, non-DC cells were shown to effectively present CNS myelin antigens to self-reactive T cells in the absence of DCs, exacerbating EAE.