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Open Access 01-12-2014 | Research

α4-integrins control viral meningoencephalitis through differential recruitment of T helper cell subsets

Authors: Veit Rothhammer, Andreas Muschaweckh, Georg Gasteiger, Franziska Petermann, Sylvia Heink, Dirk H Busch, Mathias Heikenwälder, Bernhard Hemmer, Ingo Drexler, Thomas Korn

Published in: Acta Neuropathologica Communications | Issue 1/2014

Abstract

Introduction

Natalizumab blocks α4-integrins and is a prototypic agent for a series of anti-inflammatory drugs that impair trafficking of immune cells into the CNS. However, modulation of the access of immune cells to the CNS is associated with impaired immune surveillance and detrimental viral infections of the CNS. Here, we explored the potency of cellular immune responses within the CNS to protect against viral encephalitis in mice with T cell conditional disruption of VLA-4 integrin (α4β1) expression.

Results

While VLA-4 expression in virus specific Th1 cells is non-redundant for their ability to access the CNS, α4-integrin deficient Th17 cells enter the CNS compartment and generate an inflammatory milieu upon intrathecal vaccinia virus (VV) infection. However, in contrast to Th1 cells that can adopt direct cytotoxic properties, Th17 cells fail to clear the virus due to insufficient Eomes induced perforin-1 expression.

Conclusion

The quality of the intrathecal cellular antiviral response under conditions of impaired VLA-4 function jeopardizes host protection. Our functional in vivo data extend our mechanistic understanding of anti-viral immunity in the CNS and help to estimate the risk potential of upcoming therapeutic agents that target the trafficking of immune cells into distinct anatomical compartments.

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Title: α4-integrins control viral meningoencephalitis through differential recruitment of T helper cell subsets
Authors: Veit Rothhammer
Andreas Muschaweckh
Georg Gasteiger
Franziska Petermann
Sylvia Heink
Dirk H Busch
Mathias Heikenwälder
Bernhard Hemmer
Ingo Drexler
Thomas Korn
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Acta Neuropathologica Communications / Issue 1/2014
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/2051-5960-2-27

Keynote webinar | Spotlight on medication adherence

Springer Medicine

α4-integrins control viral meningoencephalitis through differential recruitment of T helper cell subsets

Abstract

Introduction

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Results

Conclusion

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