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.
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.
Battistini
Luca
L
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia, Rome, Italy.
Piccio
Laura
L
Rossi
Barbara
B
Bach
Simona
S
Galgani
Simona
S
Gasperini
Claudio
C
Ottoboni
Linda
L
Ciabini
Donatella
D
Caramia
Maria D
MD
Bernardi
Giorgio
G
Laudanna
Carlo
C
Scarpini
Elio
E
McEver
Rodger P
RP
Butcher
Eugene C
EC
Borsellino
Giovanna
G
Constantin
Gabriela
G
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*
D000906:Antibodies; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D019010:Vascular Cell Adhesion Molecule-1