title: CD8+ T cells from patients with acute multiple sclerosis display selective increase of adhesiveness in brain venules: a critical role for P-selectin glycoprotein ligand-1.
abstract: Multiple sclerosis (MS) is considered an autoimmune inflammatory disease of the central nervous system. Under physiologic conditions, we compared the adhesiveness of CD4+ and CD8+ lymphocytes from nontreated patients with acute, relapsing-remitting multiple sclerosis (RRMS) and from healthy donors. We show that in patients with RRMS CD8+, but not with RRMS CD4+, T cells display increased rolling and arrest in inflamed murine brain venules. Moreover, CD8+, but not CD4+, lymphocytes from MS patients show increased rolling on P-selectin in vitro. Anti-P-selectin glycoprotein ligand-1 (PSGL-1) antibodies dramatically block the recruitment of CD8+ cells in brain vessels of patients with MS, suggesting that PSGL-1 represents a novel pharmaceutical target that may be exploited to block the selective entrance of CD8+ cells during early inflammation. Vascular cell adhesion molecule-1 (VCAM-1), but not PSGL-1, is critical for the adhesion of CD4+ cells in MS patients, highlighting a fundamental dichotomy in the mechanisms governing the recruitment of lymphocyte subsets in RRMS. Importantly, 7-color fluorescence-activated cell sorter (FACS) analysis, together with functional data, indicates that a large fraction of CD8+ cells from MS patients display the characteristics of memory-effector phenotype. In conclusion, our results show that CD8+, but not CD4+, T cells from patients with RRMS in the acute phase of the disease display increased ability to be recruited in inflamed brain venules.
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia, Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Battistini
authors.forename: Laura
authors.initials: L
authors.lastname: Piccio
authors.forename: Barbara
authors.initials: B
authors.lastname: Rossi
authors.forename: Simona
authors.initials: S
authors.lastname: Bach
authors.forename: Simona
authors.initials: S
authors.lastname: Galgani
authors.forename: Claudio
authors.initials: C
authors.lastname: Gasperini
authors.forename: Linda
authors.initials: L
authors.lastname: Ottoboni
authors.forename: Donatella
authors.initials: D
authors.lastname: Ciabini
authors.forename: Maria D
authors.initials: MD
authors.lastname: Caramia
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bernardi
authors.forename: Carlo
authors.initials: C
authors.lastname: Laudanna
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
authors.forename: Rodger P
authors.initials: RP
authors.lastname: McEver
authors.forename: Eugene C
authors.initials: EC
authors.lastname: Butcher
authors.forename: Giovanna
authors.initials: G
authors.lastname: Borsellino
authors.forename: Gabriela
authors.initials: G
authors.lastname: Constantin
mesh_terms: D000208:Acute Disease; D000328:Adult; D000906:Antibodies / Q000494:pharmacology; D001921:Brain / Q000098:blood supply*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002448:Cell Adhesion; D005260:Female; D005434:Flow Cytometry; D018056:Hemorheology; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000502:physiology*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology; D014699:Venules / Q000473:pathology*
chemical_list: D000906:Antibodies; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D019010:Vascular Cell Adhesion Molecule-1