Journal
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Volume 180, Issue 3, Pages 383-392Publisher
WILEY
DOI: 10.1111/cei.12590
Keywords
adhesion molecules; CD4/CD8; cerebrospinal fluid; multiple sclerosis; natalizumab; T cell ratio
Categories
Funding
- Abbott Diagnostics
- Roche Molecular Diagnostics
- Roche Diagnostics Austria
- AbbVie
- Pfizer
- Eisai
- Ever-Neuropharma
- Medtronics
- Sunovion
- New Bridge
- Gerot-Lanacher
- Biogen-Idec
- Sanovi
- Bial
- Cyberonics
- Novartis
- Actavis
- UCB Pharma
- Almirall
- Bayer
- Genzyme
- Medtronic
- Merck-Serono
- Sanofi-Aventis
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Strongly decreased leucocyte counts and a reduced CD4/CD8 T cell ratio in the cerebrospinal fluid (CSF) of natalizumab (NZB)-treated multiple sclerosis (MS) patients may have implications on central nervous (CNS) immune surveillance. With regard to NZB-associated progressive multi-focal leucoencephalopathy, we aimed at delineating a relationship between free NZB, cell-bound NZB, adhesion molecule (AM) expression and the treatment-associated shift in the CSF T cell ratio. Peripheral blood (PB) and CSF T cells from 15 NZB-treated MS patients, and CSF T cells from 10 patients with non-inflammatory neurological diseases and five newly diagnosed MS patients were studied. Intercellular adhesion molecule-1 (ICAM-1), leucocyte function antigen-1 (LFA-1), very late activation antigen-4 (VLA-4), NZB saturation levels, and T cell ratios were analysed by flow cytometry. NZB concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Lower NZB saturation levels (P<002) and a higher surface expression of ICAM-1 and LFA-1 (P<0001) were observed on CSF CD8 T cells. CSF T cell ratios (03-21) and NZB concentrations (001-042 mu g/ml) showed a pronounced interindividual variance. A correlation between free NZB, cell-bound NZB or AM expression levels and the CSF T cell ratio was not found. Extremely low NZB concentrations and a normalized CSF T cell ratio were observed in one case. The differential NZB saturation and AM expression of CSF CD8 T cells may contribute to their relative enrichment in the CSF. The reduced CSF T cell ratio appeared sensitive to steady-state NZB levels, as normalization occurred quickly. The latter may be important concerning a fast reconstitution of CNS immune surveillance.
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