Intrathecal transplantation of neural stem/precursor cells hampers the CNS-confined immune response of experimental autoimmune encephalomyelitis
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1
Università Vita-Salute San Raffaele, Italy
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2
Neuroimmunology Unit, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Hospital, Italy
Transplantation of neural stem/progenitor cells (NPCs) in experimental autoimmune encephalomyelitis (EAE) has consistently shown that NPCs promote neuroprotection through pleiotropic mechanisms, including a strong, but only partially characterized immunomodulatory effect. We investigated if and how the intrathecal transplantation of NPCs could modulate the CNS-restricted effector phase of EAE, the key event in disease initiation and maintenance.
We found that intrathecal transplantation of NPCs in MOG-immunized C57BL/6 EAE mice induced a significant and persistent amelioration of clinical disability when compared to sham treatment. At the end of follow-up, 80 days post immunization (dpi), neuropathology of NPC-transplanted mice showed lower demyelination and axonal loss. Flow cytometry analysis of CNS inflammatory infiltrate at 40 dpi revealed that these findings were preceded by a significant reduction of infiltrating myeloid cells as well as of encephalitogenic T helper cells.
Transplanted NPCs localized strategically in the meningeal perivascular spaces, in close contact with local antigen presenting cells, such as myeloid dendritic cells (DCs) and perivascular macrophages, suggesting that NPCs might interfere with the antigen-recall of autoreactive T cells within the CNS.
Indeed, in vitro co-culture of NPCs with bone marrow-derived DCs showed that NPCs inhibit, trough secreted factors, the maturation and the capability of reactivating myelin-specific T cells of DCs.
Our work confirms the efficacy of intrathecally transplanted NPCs in ameliorating EAE and suggests that NPCs can impair the antigen recall and terminal polarization of encephalitogenic T cells within the subarachnoid perivascular spaces, thus preventing CNS accumulation of infiltrating inflammatory cells responsible for disease progression.
References
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Bartholomaus, I., et al. (2009). Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions. Nature 462(7269): 94-98.
De Feo D. et al. (2012). Neural stem cell transplantation in central nervous system disorders: from cell replacement to neuroprotection. Curr Opin Neurol. 25(3):322-33.
Greter, M., et al. (2005). Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nat Med 11(3): 328-334.
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Keywords:
Neural precursor cell (NPC),
Experimental autoimmune encephalomyelitis,
Dendritic Cells,
Neuroinflammation,
cell therapy
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Translational immunology and immune intervention
Citation:
De Feo
D,
Merlini
A,
Laterza
C,
Brambilla
E,
Ruffini
F,
Comi
G and
Martino
G
(2013). Intrathecal transplantation of neural stem/precursor cells hampers the CNS-confined immune response of experimental autoimmune encephalomyelitis.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00266
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Received:
12 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Donatella De Feo, Università Vita-Salute San Raffaele, Milan, Italy, defeo.donatella@hsr.it