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Prepublished online as a Blood First Edition Paper on February 20, 2003; DOI 10.1182/blood-2002-10-3309.
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Blood, 15 June 2003, Vol. 101, No. 12, pp. 4775-4782
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
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
Luca Battistini,
Laura Piccio,
Barbara Rossi,
Simona Bach,
Simona Galgani,
Claudio Gasperini,
Linda Ottoboni,
Donatella Ciabini,
Maria D. Caramia,
Giorgio Bernardi,
Carlo Laudanna,
Elio Scarpini,
Rodger P. McEver,
Eugene C. Butcher,
Giovanna Borsellino, and
Gabriela Constantin
From the Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia, Rome; Department of Pathology, University of Verona; IRCCS Ospedale Maggiore, Milan; Department of Neurosciences, San Camillo Hospital, Rome; Department of Neurosciences, University of Tor Vergata, Rome; Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City; Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City; and Department of Pathology, Stanford University, CA.
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.
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