PD-L1+ Regulatory B Cells Are Significantly Decreased in Rheumatoid Arthritis Patients and Increase After Successful Treatment
| Autor: | Maria C. Taboada Bonfanti, Isaac I. Cadile, Carolina Lucia Montes, Sergio Manuel Alonso, Estefanía Zacca, Luisina Inés Onofrio, Maria I. Stancich, Adriana Gruppi, Eduardo Mussano, María Cecilia Ramello, Eva Virginia Acosta Rodriguez, Laura Onetti, Paola Virginia Ferrero, Cristina del Valle Acosta |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
rheumatoid arthritis CD4-Positive T-Lymphocytes Male medicine.medical_treatment Programmed Cell Death 1 Receptor Medicina Clínica CD8-Positive T-Lymphocytes B7-H1 Antigen bregs Arthritis Rheumatoid 0302 clinical medicine purl.org/becyt/ford/3.2 [https] Immunology and Allergy Cells Cultured Original Research Aged 80 and over B-Lymphocytes Regulatory Membrane Glycoproteins biology Middle Aged Reumatología Flow Cytometry Cytokine medicine.anatomical_structure Antirheumatic Agents rheumatic diseases purl.org/becyt/ford/3 [https] Female medicine.symptom lcsh:Immunologic diseases. Allergy RHEUMATIC DISEASES PD-L1 Adult medicine.medical_specialty CIENCIAS MÉDICAS Y DE LA SALUD Regulatory B cells T cell Immunology Antigens CD19 Inflammation BREGS CD19 Statistics Nonparametric 03 medical and health sciences Young Adult Immune system INFLAMMATION Internal medicine medicine Humans RHEUMATOID ARTHRITIS Aged business.industry CD24 Antigen ADP-ribosyl Cyclase 1 Coculture Techniques 030104 developmental biology Endocrinology inflammation biology.protein lcsh:RC581-607 business CD8 030215 immunology Follow-Up Studies |
| Zdroj: | Frontiers in Immunology CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET Frontiers in Immunology, Vol 9 (2018) |
| ISSN: | 1664-3224 |
| Popis: | Background: B cells play an important role in the development and maintenance of rheumatoid arthritis (RA). Although IL-10-producing B cells represent a major subset of regulatory B cells (Bregs) able to suppress autoimmune and inflammatory responses, recent reports showed that B cell-mediated immune suppression may also occur independent of IL-10. For instance, B cells can modulate T cell immune responses through the expression of regulatory molecules such as PD-L1. So far, PD-L1-expressing B cells have not been analyzed in RA patients. Objective: To analyze the frequency of PD-L1-expressing B cells in the peripheral blood of RA patients compared to healthy controls (HC) matched for sex and age, their function on T cell response and their changes in response to therapy. Methods: Fresh peripheral blood B cells from RA patients and HC were characterized by flow cytometry and their functionality assessed in a co-culture system with autologous T cells. Results: The frequencies of CD19+PD-L1+ B cells, CD24hiCD38-PD-L1+ and CD24hiCD38hiPD-L1+ B cells were significantly lower in untreated RA patients than in HC. In a follow-up study, the frequencies of PD-L1+ B cells (CD19+PD-L1+ B cells, CD24hiCD38-PD-L1+ and CD24hiCD38hiPD-L1+ B cells) increased significantly after treatment in good responder patients, although the frequency of total CD24hiCD38hi B cells decreased. CD19+ B cells from untreated RA patients and HC upregulated PD-L1 expression similarly upon stimulation with CpG plus IL-2 and were able to suppress, in vitro, CD8+ T cell proliferation and cytokine production in a PD-L1-dependent manner. Conclusions: Our results show that PD-L1+ B cells exhibiting T cell suppressive capacity are significantly decreased in untreated RA patients but increase in response to successful treatment. PD-L1 expression on B cells from RA patients can be modulated in vitro and PD-L1+ B cells could thus provide new perspectives for future treatment strategies. Fil: Zacca, Estefanía. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina Fil: Onofrio, Luisina Inés. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina Fil: Acosta, Cristina del Valle. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina Fil: Ferrero, Paola Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina Fil: Alonso, Sergio Manuel. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina Fil: Ramello, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Mussano, Eduardo Daniel Eugenio. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina Fil: Onetti, Laura. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina Fil: Cadile, Isaac I.. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina Fil: Stancich, Maria I.. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina Fil: Bonfanti, Maria C. Taboada. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina Fil: Montes, Carolina Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Acosta Rodriguez, Eva Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Gruppi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina |
| Databáze: | OpenAIRE |
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