Blood 2003 Feb 20
Battistini L, Piccio L, Rossi B, Bach S, Galgani S, Gasperini C, Ottoboni L, Ciabini D, Caramia MD, Bernardi G, Laudanna C, Scarpini E, McEver RP, Butcher EC, Borsellino G, Constantin G.
Department of Neurology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia, Rome, Italy.
Multiple Sclerosis (MS) is considered an autoimmune inflammatory disease of the central nervous system.
We compared for the first time the adhesiveness of CD4(+) and CD8(+) lymphocytes from acute, non-treated patients with the relapsing remitting form of the disease (RRMS) and from healthy donors under physiological conditions.
We show that in patients with RRMS CD8(+), but not 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 from MS patients in brain vessels, suggesting that PSGL-1 represents a novel pharmaceutical target which may be exploited to block the selective entrance of CD8(+) cells during early inflammation.
VCAM-1, but not PSGL-1, is critical for the adhesion of CD4(+) cells from MS patients, highlighting a fundamental dichotomy in the mechanisms governing the recruitment of lymphocyte subsets in RRMS.
Importantly, seven-colour 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.