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.

Costimulatory pathways in multiple sclerosis : distinctive expression of PD-1 and PD-L1 in patients with different patterns of disease / D. Trabattoni, M. Saresella, M. Pacei, I. Marventano, L. Mendozzi, M. Rovaris, D. Caputo, M. Borelli, M. Clerici. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 183:8(2009), pp. 4984-4993. [10.4049/jimmunol.0901038]

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

D. Trabattoni
Primo
;
M. Pacei;M. Borelli
Penultimo
;
M. Clerici
Ultimo
2009

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.
Settore MED/04 - Patologia Generale
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/71393
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