Macrophage-independent T cell infiltration to the site of injury-induced brain inflammation

Fux, Michaela; van Rooijen, Nico; Owens, Trevor (2008). Macrophage-independent T cell infiltration to the site of injury-induced brain inflammation. Journal of neuroimmunology, 203(1), pp. 64-72. Amsterdam: Elsevier 10.1016/j.jneuroim.2008.06.025

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We have addressed the role of macrophages in glial response and T cell entry to the CNS after axonal injury, by using intravenous injection of clodronate-loaded mannosylated liposomes, in C57BL6 mice. As expected, clodronate-liposome treatment resulted in depletion of peripheral macrophages which was confirmed by F4/80- and MOMA-1(-) stainings in spleen. Sequential clodronate-liposome treatment 4, 2 and 0 days before axotomy resulted in significant reduction of infiltrating CD45(high) CD11b+ macrophages in the hippocampus at 1, 2 and 3 days post-lesion, measured by flow cytometry. There was a slight delay in the expansion of CD45(dim) CD11+ microglia in clodronate-liposome treated mice, but macrophage depletion had no effect on the percentage of infiltrating T cells in the lesion-reactive hippocampus. Lesion-induced TNFalpha mRNA expression was not affected by macrophage depletion, suggesting that activated glial cells are the primary source of this cytokine in the axonal injury-reactive brain. This identifies a potentially important distinction from inflammatory autoimmune infiltration in EAE, where macrophages are a prominent source of TNFalpha and their depletion prevents parenchymal T cell infiltration and disease.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute for Immunology (discontinued)

UniBE Contributor:

Fux, Michaela

ISSN:

0165-5728

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:13

Last Modified:

17 Mar 2015 22:33

Publisher DOI:

10.1016/j.jneuroim.2008.06.025

PubMed ID:

18653241

Web of Science ID:

000260695200009

URI:

https://boris.unibe.ch/id/eprint/32342 (FactScience: 197442)

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