Phenotypic and functional analysis of T cells homing into the CSF of subjects with inflammatory diseases of the CNS.
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-gamma-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.
Giunti
Debora
D
Neuroimmunology Unit, Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Italy.
Borsellino
Giovanna
G
Benelli
Roberto
R
Marchese
Monica
M
Capello
Elisabetta
E
Valle
Maria Teresa
MT
Pedemonte
Enrico
E
Noonan
Douglas
D
Albini
Adriana
A
Bernardi
Giorgio
G
Mancardi
Giovanni Luigi
GL
Battistini
Luca
L
Uccelli
Antonio
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation; D002465:Cell Movement; D054415:Chemokine CCL19; D054357:Chemokine CXCL10; D054377:Chemokine CXCL12; D019742:Chemokines, CC / Q000096:biosynthesis / Q000235:genetics; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004660:Encephalitis / Q000134:cerebrospinal fluid / Q000276:immunology; D005260:Female; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000032:analysis; D020852:Lyme Neuroborreliosis / Q000134:cerebrospinal fluid / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008581:Meningitis / Q000134:cerebrospinal fluid / Q000276:immunology; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000276:immunology; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000134:cerebrospinal fluid / Q000276:immunology; D019713:Receptors, CCR5 / Q000032:analysis; D054400:Receptors, CCR7; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis
C515460:CCL19 protein, human; C515370:CCR7 protein, human; C515255:CXCL12 protein, human; C515187:CXCR3 protein, human; D054415:Chemokine CCL19; D054357:Chemokine CXCL10; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019743:Chemokines, CXC; D019713:Receptors, CCR5; D054400:Receptors, CCR7; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens