Journal Article

Differential immune cell dynamics in the CNS cause CD4<sup>+</sup> T cell compartmentalization

Volker Siffrin, Alexander U. Brandt, Helena Radbruch, Josephine Herz, Nadia Boldakowa, Tina Leuenberger, Johannes Werr, Astrid Hahner, Ulf Schulze-Topphoff, Robert Nitsch and Frauke Zipp

in Brain

Published on behalf of The Guarantors of Brain

Volume 132, issue 5, pages 1247-1258
Published in print May 2009 | ISSN: 0006-8950
Published online January 2009 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awn354
Differential immune cell dynamics in the CNS cause CD4+ T cell compartmentalization

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In the course of autoimmune CNS inflammation, inflammatory infiltrates form characteristic perivascular lymphocyte cuffs by mechanisms that are not yet well understood. Here, intravital two-photon imaging of the brain in anesthetized mice, with experimental autoimmune encephalomyelitis, revealed the highly dynamic nature of perivascular immune cells, refuting suggestions that vessel cuffs are the result of limited lymphocyte motility in the CNS. On the contrary, vessel-associated lymphocyte motility is an actively promoted mechanism which can be blocked by CXCR4 antagonism. In vivo interference with CXCR4 in experimental autoimmune encephalomyelitis disrupted dynamic vessel cuffs and resulted in tissue-invasive migration. CXCR4-mediated perivascular lymphocyte movement along CNS vessels was a key feature of CD4+ T cell subsets in contrast to random motility of CD8+ T cells, indicating a dominant role of the perivascular area primarily for CD4+ T cells. Our results visualize dynamic T cell motility in the CNS and demonstrate differential CXCR4-mediated compartmentalization of CD4+ T-cell motility within the healthy and diseased CNS.

Keywords: T cells; compartmentalization; two-photon microscopy; CXCR4; EAE/MS

Journal Article.  7369 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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