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

Autor: Luu T; Department of Microbiology & Immunology, Penn State College of Medicine, Hershey, Pennsylvania, United States of America., Cheung JF; Department of Microbiology & Immunology, Penn State College of Medicine, Hershey, Pennsylvania, United States of America., Baccon J; Department of Pathology, Penn State College of Medicine, Hershey, Pennsylvania, United States of America.; Department of Neurosurgery, Penn State College of Medicine, Hershey, Pennsylvania, United States of America., Waldner H; Department of Microbiology & Immunology, Penn State College of Medicine, Hershey, Pennsylvania, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2021 Apr 23; Vol. 16 (4), pp. e0250340. Date of Electronic Publication: 2021 Apr 23 (Print Publication: 2021).
DOI: 10.1371/journal.pone.0250340
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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