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Updated: Aug 23, 2026
Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
Published on: May 18, 2018
Initiation of immune responses in brain is promoted by local dendritic cells
Jozsef Karman1, Changying Ling, Matyas Sandor
1Cellular and Molecular Pathology Program, University of Wisconsin, Madison 53706, USA.
Insights
Dendritic cells (DCs) migrate from the brain to lymph nodes, initiating T cell responses. These activated T cells can then home back to the central nervous system (CNS).
Area of Science:
- Neuroimmunology
- Cellular Immunology
Background:
- The role of dendritic cells (DCs) in initiating T cell responses and T cell homing to the central nervous system (CNS) remains unclear.
- Understanding antigen-presenting cell (APC) migration is crucial for neuroimmune research.
Purpose of the Study:
- To investigate the migration of DCs from the CNS and their role in T cell activation and homing.
- To determine if CNS-emigrant DCs can initiate adaptive immune responses and direct T cell homing to the brain.
Main Methods:
- Confocal microscopy and flow cytometry to identify and track antigen-presenting cells (APCs) in the brain.
- Differentiating green fluorescent protein (GFP)-transgenic mouse bone marrow-derived DCs and injecting them into naive mouse brains.
- Tracking DC migration pathways from the brain to peripheral lymphoid organs.
- Assessing T cell responses using tetramer staining and LFA-1 activation marker staining after antigen challenge.
Main Results:
- Cells expressing CD11c, CD205, and MHC class II molecules accumulate at intracerebral antigen injection sites.
- DCs migrate from the brain to cervical lymph nodes, a process inhibitable by fixation or pertussis toxin.
- Intracerebral injection of OVA-loaded DCs induces SIINFEKL-specific T cell responses in lymph nodes and spleen.
- Activated T cells subsequently home to the CNS, but this homing is not induced by intravenous DC injection alone.
Conclusions:
- Brain-emigrant DCs are sufficient to promote T cell homing to the CNS.
- Initiation of immune responses against CNS antigens involves APC migration from neural tissue to peripheral lymphoid organs.
- This migration mechanism is similar to that observed in other organ systems.
Abstract:
The contribution of dendritic cells (DCs) to initiating T cell-mediated immune response in and T cell homing into the CNS has not yet been clarified. In this study we show by confocal microscopy and flow cytometry that cells expressing CD11c, CD205, and MHC class II molecules and containing fluorescently labeled, processed Ag accumulate at the site of intracerebral Ag injection. These cells follow a specific pattern upon migrating out of the brain. To track their pathway out of the CNS, we differentiated DCs from bone marrow of GFP-transgenic mice and injected them directly into brains of naive C57BL/6 mice. We demonstrate that DCs migrate from brain to cervical lymph nodes, a process that can be blocked by fixation or pertussis toxin treatment of the DCs. Injection of OVA-loaded DCs into brain initiates a SIINFEKL (a dominant OVA epitope)-specific T cell response in lymph nodes and spleen, as measured by specific tetramer and LFA-1 activation marker staining. Additionally, a fraction of activated SIINFEKL-specific T cells home to the CNS. Specific T cell homing to the CNS, however, cannot be induced by i.v. injection of OVA-loaded DCs alone. These data suggest that brain-emigrant DCs are sufficient to support activated T cells to home to the tissue of DC origination. Thus, initiation of immune reactivity against CNS Ags involves the migration of APCs from nervous tissue to peripheral lymphoid tissues, similarly to that in other organs.
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