Decrease in the Numbers of Dendritic Cells and CD4+ T Cells in Cerebral Perivascular Spaces Due to Natalizumab

Maria DEL PILAR MARTIN; Petra D CRAVENS; B. K KLEINSCHMIDT-DEMASTERS; Olaf STÜVE; Ryan WINGER; Elliot M FROHMAN; Michael K RACKE; Todd N EAGAR; Scott S ZAMVIL; Martin S WEBER; Bernhard HEMMER; Nitin J KARANDIKAR

doi:10.1001/archneur.65.12.noc80051

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Decrease in the Numbers of Dendritic Cells and CD4+ T Cells in Cerebral Perivascular Spaces Due to Natalizumab

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Decrease in the Numbers of Dendritic Cells and CD4+ T Cells in Cerebral Perivascular Spaces Due to Natalizumab

Maria DEL PILAR MARTIN, Petra D CRAVENS, B. K KLEINSCHMIDT-DEMASTERS, Olaf STÜVE, Ryan WINGER, Elliot M FROHMAN, Michael K RACKE, Todd N EAGAR, Scott S ZAMVIL, Martin S WEBER, …

Archives of neurology (Chicago), Vol.65(12), pp.1596-1603

2008

DOI: 10.1001/archneur.65.12.noc80051

PMID: 18852339

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Abstract

Objective: To extend our studies on the prolonged and differential effect of natalizumab on T lymphocyte numbers in the cerebrospinal fluid, we investigated the number and phenotypes of leukocytes and the expression of major histocompatibility complex (MHC) classes I and II in cerebral perivascular spaces (CPVS). We hypothesized that natalizumab reduces the number of antigen presenting cells in CPVS. Design: A case-control study in which inflammatory cell numbers in the CPVS of cerebral tissue were assessed by immunohistochemical staining. Subjects: A patient with multiple sclerosis (MS) who developed progressive multifocal leukoencephalopathy (PML) during natalizumab therapy. Controls included location-matched cerebral autopsy material of patients without disease of the central nervous system, patients with MS not treated with natalizumab, and patients with PML not associated with natalizumab therapy. Results: The absolute number of CPVS in the patient with MS treated with natalizumab was significantly lower than in the control groups owing to extensive destruction of the tissue architecture. The expression of MHC class II molecules and the number of CD209+ dendritic cells were significantly decreased in the CPVS of the patient with MS treated with natalizumab. No CD4+ T cells were detectable. Conclusions: Our observations may explain the differential and prolonged effects of natalizumab therapy on leukocyte numbers in the cerebrospinal fluid.

Neurology

Fundamental and applied biological sciences. Psychology

Vertebrates: nervous system and sense organs

Biological and medical sciences

Development. Senescence. Regeneration. Transplantation

Medical sciences

Details

Title: Subtitle: Decrease in the Numbers of Dendritic Cells and CD4+ T Cells in Cerebral Perivascular Spaces Due to Natalizumab
Creators: Maria DEL PILAR MARTIN - Department of Neurology, University of Texas Southwestern Medical Center, Dallas, United States
Petra D CRAVENS - Department of Neurology, University of Texas Southwestern Medical Center, Dallas, United States
B. K KLEINSCHMIDT-DEMASTERS - Departments of Pathology, Neurology, and Neurosurgery, University of Colorado, Denver, United States
Olaf STÜVE - Department of Neurology, University of Texas Southwestern Medical Center, Dallas, United States
Ryan WINGER - Department of Neurology, University of Texas Southwestern Medical Center, Dallas, United States
Elliot M FROHMAN - Department of Neurology, University of Texas Southwestern Medical Center, Dallas, United States
Michael K RACKE - Departments of Neurology, The Ohio State University Medical Center, Columbus, United States
Todd N EAGAR - Department of Neurology, University of Texas Southwestern Medical Center, Dallas, United States
Scott S ZAMVIL - University of California, San Francisco, United States
Martin S WEBER - University of California, San Francisco, United States
Bernhard HEMMER - Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
Nitin J KARANDIKAR - Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States
Resource Type: Journal article
Publication Details: Archives of neurology (Chicago), Vol.65(12), pp.1596-1603
DOI: 10.1001/archneur.65.12.noc80051
PMID: 18852339
NLM abbreviation: Arch Neurol
ISSN: 0003-9942
eISSN: 1538-3687
Publisher: American Medical Association; Chicago, IL
Language: English
Date published: 2008
Academic Unit: Pathology
Record Identifier: 9984047727802771

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