NDLI: Costimulatory pathways in multiple sclerosis: distinctive expression of PD-1 and PD-L1 in patients with different patterns of disease.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Saresella, Marina Borelli, Manuela Trabattoni, Daria Pacei, Michela Caputo, Domenico Rovaris, Marco Clerici, Mario Marventano, Ivana Mendozzi, Laura
Description	Country affiliation: Italy Author Affiliation: Trabattoni D ( Department of Immunology, University of Milano, Milan, Italy.)
Abstract	T lymphocytes costimulatory molecules, including CD80, CD86, CD28, CTLA4, PD-1, PD-L1, and B7-H3, are associated with the preferential production of pro- or anti-inflammatory cytokines. We analyzed the expression of these molecules and myelin basic protein (MBP)-specific IL-10 and IFN-gamma production in patients with multiple sclerosis (MS) with relapsing-remitting acute (AMS, n = 40) or stable (SMS, n = 38). Twenty-two patients successfully undergoing therapy with glatimer acetate (n = 12) or IFNbeta (n = 10) were also analyzed. MBP-specific and PD-1-expressing T lymphocytes, PD-L1-expressing CD19(+) cells, and PD-L1(+)/IL-10(+)/CD14(+) and CD19(+) cells were significantly augmented in SMS patients. Additionally, MBP-specific and annexin V-expressing CD4(+) and CD8(+) (apoptotic) T lymphocytes were augmented and pAkt-positive (proliferating) cells were decreased in SMS compared with AMS patients. PD-1 ligation resulted in the increase of pAkt(+) lymphocytes in AMS patients alone. B7-H3 expression and IFN-gamma production were comparable in all individuals but the PD-L1(+)/IL-10(+) over B7-H3(+)/IFN-gamma(+) ratio was significantly lower in AMS compared with SMS patients. Finally, PD-L1 expression on immune cells was reduced in treated patients, suggesting that therapy-induced disease remission is not associated with the modulation of the expression of this molecule. The PD-1/PD-L1 pathway plays an important role in modulating immune functions in MS patients; monitoring and targeting these proteins could offer diagnostic and therapeutic advantages.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	8
Volume Number	183
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2009-10-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antigens, Cd Immunology Apoptosis Regulatory Proteins Multiple Sclerosis T-lymphocytes Metabolism Antigens, Cd274 Antigens, Cd28 Antigens, Cd80 Antigens, Cd86 Apoptosis B7 Antigens Ctla-4 Antigen Interferon-gamma Interleukin-10 Myelin Basic Protein Oncogene Protein V-akt Peptides Programmed Cell Death 1 Receptor Receptors, Immunologic Signal Transduction Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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