Decrease in the numbers of dendritic cells and CD4+ T cells in cerebral perivascular spaces due to natalizumab.
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.


METHODS
A case-control study in which inflammatory cell numbers in the CPVS of cerebral tissue were assessed by immunohistochemical staining.


METHODS
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.
del Pilar Martin
Maria
M
Department of Neurology, University of Texas Southwestern Medical Center at Dallas, Neurology Section, Veterans Affairs North Texas Health Care System, Medical Service, 4500 S Lancaster Rd, Dallas, TX 75216, USA.
Cravens
Petra D
PD
Winger
Ryan
R
Frohman
Elliot M
EM
Racke
Michael K
MK
Eagar
Todd N
TN
Zamvil
Scott S
SS
Weber
Martin S
MS
Hemmer
Bernhard
B
Karandikar
Nitin J
NJ
Kleinschmidt-DeMasters
B K
BK
Stüve
Olaf
O
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D016022:Case-Control Studies; D002452:Cell Count / Q000379:methods; D002552:Cerebral Ventricles / Q000187:drug effects / Q000473:pathology*; D003713:Dendritic Cells / Q000187:drug effects*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications; D000069442:Natalizumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D000069442:Natalizumab