Enhanced Programmed Death 1 and Diminished Programmed Death Ligand 1 Up-Regulation Capacity of Post-Activated Lupus B Cells.
Journal
Arthritis & rheumatology (Hoboken, N.J.)
ISSN: 2326-5205
Titre abrégé: Arthritis Rheumatol
Pays: United States
ID NLM: 101623795
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
07
11
2018
accepted:
19
03
2019
pubmed:
29
3
2019
medline:
6
2
2020
entrez:
29
3
2019
Statut:
ppublish
Résumé
To assess the expression of programmed death 1 (PD-1), PD ligand 1 (PD-L1), and PD-L2 by B cells from patients with systemic lupus erythematosus (SLE) at baseline and after in vitro stimulation and to analyze their functional relationship to B cell proliferation. Peripheral blood mononuclear cells obtained from 29 SLE patients and 27 healthy donors were stimulated with interleukin-2 (IL-2)/IL-10, anti-B cell receptor (anti-BCR), CpG, and CD40L alone or in combination. Expression of PD-1, PD-L1, and PD-L2 on defined B cell subsets as well as on CD3+ T cells was analyzed by flow cytometry at baseline and after 48 hours of stimulation. Additionally, after 48 hours of stimulation, CD71 was evaluated as a proliferation marker on CD19+CD20+ B cells. Increased PD-1 expression was characteristic of unstimulated lupus B cells and T cells. Upon stimulation of B cells with IL-2/IL-10, anti-BCR, CpG, and CD40L for 48 hours, the capacity of SLE B cells to up-regulate PD-L1 expression was substantially diminished (P = 0.0006) along with reduced B cell proliferation (P = 0.0039). Reduced PD-L1 expression was inversely correlated with the presence of the interferon signature (r = -0.8571, P < 0.0001) and the clinical SLE Disease Activity Index score (r = -0.5696, P = 0.0087). Post-activated, hyporesponsive lupus B cells are characterized by a phenotype of increased PD-1, functionally diminished PD-L1 up-regulation capacity, and reduced proliferation upon stimulation.
Substances chimiques
B7-H1 Antigen
0
CD274 protein, human
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1539-1544Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : DFG DO491/10/1
Pays : International
Organisme : Deutsche Forschungsgemeinschaft
ID : DFG DO491/7/3
Pays : International
Organisme : Deutsche Forschungsgemeinschaft
ID : TR 130
Pays : International
Informations de copyright
© 2019, American College of Rheumatology.
Références
Schrezenmeier E, Weissenßerg SY, Stefanski AL, Szelinski F, Wiedemann A, Lino AC, et al. Postactivated B cells in systemic lupus erythematosus: update on translational aspects and therapeutic considerations. Curr Opin Rheumatol 2019;31:175-84.
Chamoto K, Al-Habsi M, Honjo T. Role of PD-1 in immunity and diseases. Curr Top Microbiol Immunol 2017;410:75-97.
Van der Vlist M, Kuball J, Radstake TR, Meyaard L. Immune checkpoints and rheumatic diseases: what can cancer immunotherapy teach us? Nat Rev Rheumatol 2016;12:593-604.
Bertsias GK, Nakou M, Choulaki C, Raptopoulou A, Papadimitraki E, Goulielmos G, et al. Genetic, immunologic, and immunohistochemical analysis of the programmed death 1/programmed death ligand 1 pathway in human systemic lupus erythematosus. Arthritis Rheum 2009;60:207-18.
Nishimura H, Nose M, Hiai H, Minato N, Honjo T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 1999;11:141-51.
Wong M, La Cava A, Hahn BH. Blockade of programmed death-1 in young (New Zealand black × New Zealand white)F1 mice promotes the suppressive capacity of CD4+ regulatory T cells protecting from lupus-like disease. J Immunol 2013;190:5402-10.
Liao W, Zheng H, Wu S, Zhang Y, Wang W, Zhang Z, et al. The systemic activation of programmed death 1-PD-L1 axis protects systemic lupus erythematosus model from nephritis. Am J Nephrol 2017;46:371-9.
Hochberg MC, for the Diagnostic and Therapeutic Criteria Committee of the American College of Rheumatology. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus [letter]. Arthitis Rheum 1997;40:1725.
Rose T, Grützkau A, Hirseland H, Huscher D, Dähnrich C, Dzionek A, et al. IFNα and its response proteins, IP-10 and SIGLEC-1, are biomarkers of disease activity in systemic lupus erythematosus. Ann Rheum Dis 2013;72:1639-45.
Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang DH, and the Committee on Prognosis Studies in SLE. Derivation of the SLEDAI: a disease activity index for lupus patients. Arthritis Rheum 1992; 35:630-40.
Motamedi M, Xu L, Elahi S. Correlation of transferrin receptor (CD71) with Ki67 expression on stimulated human and mouse T cells: the kinetics of expression of T cell activation markers. J Immunol Methods 2016;437:43-52.
Liu MF, Weng CT, Weng MY. Variable increased expression of program death-1 and program death-1 ligands on peripheral mononuclear cells is not impaired in patients with systemic lupus erythematosus. J Biomed Biotechnol 2009;2009:406136.
Jenks SA, Cashman KS, Zumaquero E, Marigorta UM, Patel AV, Wang X, et al. Distinct effector B cells induced by unregulated Toll-like receptor 7 contribute to pathogenic responses in systemic lupus erythematosus. Immunity 2018;49:725-39.
Wang S, Wang J, Kumar V, Karnell JL, Naiman B, Gross PS, et al. IL-21 drives expansion and plasma cell differentiation of autoreactive CD11chiT-bet+ B cells in SLE. Nat Commun 2018;9:1758.
McKinney EF, Lee JC, Jayne DR, Lyons PA, Smith KG. T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection. Nature 2015;523:612-6.
Shi J, Hou S, Fang Q, Liu X, Liu X, Qi H. PD-1 controls follicular T helper cell positioning and function. Immunity 2018;49:264-74.