* Neuroimmunology Unit, Department of Neurosciences, Ophthalmology and Genetics, and
Centre of Excellence for Biomedical Research, University of Genoa, Italy;
Laboratory of Neuroimmunology, IRCCS, S. Lucia, Rome, Italy;
Molecular Biology Laboratory and
# Tumor Progression Section, National Cancer Research Institute, Genoa, Italy;
¶ II Division of Haematology, S. Martino Hospital, Genoa, Italy; and
** Department of Neuroscience, University of Rome "Tor Vergata," Italy
Correspondence: Antonio Uccelli, M.D., Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Via De Toni 5, 16132, Genoa, Italy. E-mail: auccelli{at}neurologia.unige.it
The recruitment of lymphocytes across the blood brain barrier (BBB) is mediated by adhesion molecules and chemokines. The expression of activation markers and of chemokine receptors on T cells homing to the nervous system (NS) may help define their functional state. In the cerebrospinal fluid (CSF) of subjects with inflammatory neurological diseases (IND), including multiple sclerosis, we observed an increased number of T cells coexpressing CXCR3 and CCR5 as well as T cells with a CD45RO+ CCR7+ CD27+ memory phenotype. A subset of CCR7+ T cells coexpressed CXCR3 and CCR5. We also detected an increased number of interferon-
-producing T cells in the CSF compared with peripheral blood, mostly but not exclusively in the CD45RO+ CCR7- CD27- compartment. T helper 1 (Th1) clones, established from the CSF of individuals with IND and from a healthy subject, similarly migrated to CXCL10, CXCL12, and CCL5. CXCL10, CXCL12, and CCL19 were increased in the CSF of individuals with neuroinflammation. These findings suggest that CSF is enriched in Th1-polarized memory T cells capable of differentiating into effector cells upon antigen encounter. These cells are recruited into the CSF by inducible chemokines. Thus, CSF represents a transitional station for T cells trafficking to and from the NS.
Key Words: MS • chemokines • T lymphocytes • neuroimmunology • cell trafficking
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