CD4+CD25+FoxP3+PD1– regulatory T cells in acute and stable relapsing-remitting multiple sclerosis and their modulation by therapy Marina Saresella * , Ivana Marventano * , Renato Longhi ‡ , Francesca Lissoni § , Daria Trabattoni § , Laura Mendozzi † , Domenico Caputo † and Mario Clerici * ,|| ,1 * Laboratory of Molecular Medicine and Biotechnology and † Multiple Sclerosis Unit, Don C. Gnocchi ONLUS Foundation, IRCCS, Milan, Italy; ‡ ICRM-CNR, Milan, Italy; and § DISP LITA Vialba and || Department of Biomedical Sciences and Technologies, University of Milan, Milan, Italy 1 Correspondence: Department of Biomedical Sciences and Technologies, University of Milan, Via Fratelli Cervi 93, 20090 Segrate (Milan), Italy. E-mail: mario.clerici@unimi.it The intracellular expression of the programmed death receptor 1 (PD1) identifies a subset of naive T reg cells with enhanced suppressive ability; antigen stimulation results in the surface expression of PD1. Because the role of T reg impairments in multiple sclerosis (MS) is still contradictory, we analyzed naive PD1– and PD1+ T reg cells in peripheral blood and cerebrospinal fluid (CSF) of relapsing-remitting multiple sclerosis (RR-MS) patients and of healthy control subjects. Results showed that 1 ) CSF PD1– T reg cells were significantly augmented in MS patients; 2 ) PD1– T reg cells were significantly increased in the peripheral blood of patients with stable disease (SMS) compared to those with acute (AMS) disease, and in patients responding to glatiramer acetate (COPA) compared to AMS- and COPA-unresponsive patients; and 3) PD1+ T reg cells were similar in CSF and peripheral blood of all groups analyzed. PD1– T reg cells were not increased in the peripheral blood of interferon-β (IFNβ) -responsive patients, but the suppressive ability of T reg cells was significantly higher in SMS and in COPA- or IFNβ-responsive compared to AMS- and COPA-unresponsive individuals. The data herein suggest that PD1– T reg cells play a pivotal role in MS and offer a biological explanation for disease relapse and for the mechanism associated with response to COPA and IFNβ.—Saresella, M., Marventano, I., Longhi, R., Lissoni, F., Trabattoni, D., Mendozzi, L., Caputo, D., Clerici, M. CD4+CD25+FoxP3+PD1– regulatory T cells in acute and stable relapsing-remitting multiple sclerosis and their modulation by therapy. Key Words: immunology • T lymphocytes • glatiramer acetate • copaxone • neurology
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CD4+CD25+FoxP3+PD1– regulatory T cells in acute and stable relapsing-remitting multiple sclerosis and their modulation by therapy
Saresella, Marina; Marventano, Ivana; Longhi, Renato; Lissoni, Francesca; Trabattoni, Daria; Mendozzi, Laura; Caputo, Domenico; Clerici, Mario
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, Volume 22 (10): 3500
Fed of American Socs for Experimental Biology – Oct 1, 2008
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