Am J Pathol. 2000 Dec;157(6):1991-2002.

Intracerebral recruitment and maturation of dendritic cells in the onset and progression of experimental autoimmune encephalomyelitis.

Serafini B, Columba-Cabezas S, Di Rosa F, Aloisi F.

Source

Laboratory of Organ and System Pathophysiology, Istituto Superiore di Sanità, Rome, Italy.

Abstract

Dendritic cells (DCs) are thought to be key elements in the initiation and maintenance of autoimmune diseases. In this study, we sought evidence that DCs recruited to the central nervous system (CNS), a site that is primarily devoid of resident DCs, play a role in the effector phase and propagation of the immune response in experimental autoimmune encephalomyelitis (EAE). After immunization of SJL mice with proteolipid protein 139-151 peptide, process-bearing cells expressing the DC markers DEC-205 and CD11c appeared early in the spinal cord. During acute, chronic, and relapsing EAE, DEC-205(+) DCs expressing a lymphostimulatory phenotype (including the mature DC marker MIDC-8, major histocompatibility complex class II, CD40, and CD86 molecules) accumulated within the CNS inflammatory cell infiltrates. More prominent infiltration of the spinal cord parenchyma by mature DCs was observed in mice with relapsing disease. Macrophage inflammatory protein 3alpha, a chemokine active on DCs and lymphocytes, and its receptor CCR6 were up-regulated in the CNS during EAE. These findings suggest that intracerebral recruitment and maturation of DCs may be crucial in the local stimulation and maintenance of autoreactive immune responses, and that therapeutic strategies aimed at manipulating DC migration could be useful in the treatment of CNS autoimmune disorders.

PMID:: 11106572; [PubMed - indexed for MEDLINE]
PMCID:: PMC1885753

Free PMC Article

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Figure 1.

Localization of DC markers in the CNS of normal SJL mice (A–C) and of mice immunized with PLP 139-151 in CFA before the onset of EAE clinical signs (day 10 after immunization) (D–H). Representative cerebellar (A) and thoracic spinal cord (B–H) sections are shown. CNS sections were stained for the indicated markers and visualized with DAB, as described in Materials and Methods. Control CNS: DEC-205⁺ process-bearing cells in the choroid plexus of the fourth ventricle (A), DEC-205⁺ (B) and CD11c⁺ (C) process-bearing cells in the spinal cord meninges. Preclinical EAE: DEC-205⁺ (D and E), CD11c⁺ (F), and MHC class II⁺ (H) cells with thin cytoplasmic processes are present in the subpial white matter of the ventral and lateral spinal cord. Note the ramified morphology of a DEC-205⁺ cell immediately beneath the pial surface (inset in E). Double staining with anti-CD11b (brown color, DAB) and anti-CD11c (red color, fuchsin) mAbs reveals that CD11c mAb recognizes intraparenchymal cells that are distinct from CD11b⁺ microglia (G). Original magnifications: ×500 (A, D, F, and H), ×1000 (B, C, E, and G), and ×1575 (inset).

Intracerebral Recruitment and Maturation of Dendritic Cells in the Onset and Progression of Experimental Autoimmune Encephalomyelitis