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

Area of Science:

• Neuroimmunology
• Immunology
• Neurology

Background:

• Natalizumab is a monoclonal antibody used to treat multiple sclerosis (MS).
• Its effects on leukocyte populations in the cerebrospinal fluid (CSF) are prolonged and differential.
• Understanding its impact on the central nervous system (CNS) microenvironment is crucial.

Purpose of the Study:

• To investigate the effect of natalizumab on leukocyte numbers and phenotypes in cerebral perivascular spaces (CPVS).
• To examine the expression of major histocompatibility complex (MHC) classes I and II in CPVS.
• To test the hypothesis that natalizumab reduces antigen-presenting cells in CPVS.

Main Methods:

• A case-control study design was employed.
• Immunohistochemical staining was used to assess inflammatory cell numbers in CPVS of cerebral tissue.
• Analysis included a natalizumab-treated MS patient who developed PML, alongside various control groups.

Main Results:

• The number of CPVS was significantly lower in the natalizumab-treated MS patient compared to controls.
• Expression of MHC class II molecules and CD209+ dendritic cells were significantly decreased in CPVS.
• No CD4+ T cells were detected in the CPVS of the treated patient.

Conclusions:

• Natalizumab significantly reduces antigen-presenting cells and MHC class II expression within CPVS.
• These findings may elucidate the prolonged and differential impact of natalizumab on CSF leukocyte counts.
• The study provides insights into natalizumab's mechanism of action in the CNS.