title: iNKT and memory B-cell alterations in HHV-8 multicentric Castleman disease.
abstract: Human herpesvirus 8 (HHV-8) is the causative agent of Kaposi sarcoma (KS) and multicentric Castleman disease (MCD), a life-threatening, virally induced B-cell lymphoproliferative disorder. HHV-8 is a B-lymphotropic γ-herpesvirus closely related to the Epstein-Barr virus (EBV). Invariant natural killer T (iNKT) cells are innate-like T cells that play a role in antiviral immunity, specifically in controlling viral replication in EBV-infected B cells. Decline of iNKT cells is associated with age or HIV infection, both situations associated with HHV-8-related diseases. We analyzed iNKT cells in both blood (n = 26) and spleen (n = 9) samples from 32 patients with HHV-8 MCD and compared them with patients with KS (n = 24) and healthy donors (n = 29). We determined that both circulating and splenic iNKT cell frequencies were markedly decreased in patients with HHV-8 MCD and were undetectable in 6 of them. Moreover, iNKT cells from patients with HHV-8 MCD displayed a proliferative defect after stimulation with α-galactosylceramide. These iNKT cell alterations were associated with an imbalance in B-cell subsets, including a significant decrease in memory B cells, particularly of marginal zone (MZ) B cells. Coculture experiments revealed that the decrease in iNKT cells contributed to the alterations in the B-cell subset distribution. These observations contribute to a better understanding of the complex interactions between HHV-8 and immune cells that cause HHV-8-related MCD.
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Université Paris 06, INSERM, Centre d'Immunologie et des Maladies Infectieuses, Unité Mixte de Recherche (UMR) 1135, Équipes de Recherche Labellisées Centre National de la Recherche Scientifique (CNRS) 8255, Paris, France.
authors.forename: Zineb
authors.initials: Z
authors.lastname: Sbihi
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Université Paris 06, INSERM, Centre d'Immunologie et des Maladies Infectieuses, Unité Mixte de Recherche (UMR) 1135, Équipes de Recherche Labellisées Centre National de la Recherche Scientifique (CNRS) 8255, Paris, France.|Hôpital Bichat, Médecine Interne, Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Dossier
authors.affiliation: Hôpital Saint-Louis, Immunologie Clinique, Equipe d'Accueil 3518, Université Paris Diderot Paris 7, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Boutboul
authors.affiliation: Hôpital Saint-Louis, Immunologie Clinique, Equipe d'Accueil 3518, Université Paris Diderot Paris 7, Paris, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Galicier
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Université Paris 06, INSERM, Centre d'Immunologie et des Maladies Infectieuses, Unité Mixte de Recherche (UMR) 1135, Équipes de Recherche Labellisées Centre National de la Recherche Scientifique (CNRS) 8255, Paris, France.|Département d'Immunologie, CHU Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Parizot
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Université Paris 06, INSERM, Centre d'Immunologie et des Maladies Infectieuses, Unité Mixte de Recherche (UMR) 1135, Équipes de Recherche Labellisées Centre National de la Recherche Scientifique (CNRS) 8255, Paris, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Emarre
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, Unité Mixte de Service 30, l'Unité Mixte Imagerie et Cytométrie, Plateforme Cytométrie Pitié-Salpêtrière, Paris, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Hoareau
authors.affiliation: Service de Dermatologie, Hôpital Cochin, APHP et Institut Cochin U1016 INSERM, Université Paris Descartes, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dupin
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, INSERM, UMR 1136, Paris, France.|Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, Service de Virologie, CHU Pitié-Salpêtrière, APHP, Paris, France; and.
authors.forename: Anne-Geneviève
authors.initials: AG
authors.lastname: Marcelin
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Université Paris 06, INSERM, Centre d'Immunologie et des Maladies Infectieuses, Unité Mixte de Recherche (UMR) 1135, Équipes de Recherche Labellisées Centre National de la Recherche Scientifique (CNRS) 8255, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Oudin
authors.affiliation: Hôpital Saint-Louis, Immunologie Clinique, Equipe d'Accueil 3518, Université Paris Diderot Paris 7, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Fieschi
authors.affiliation: Hôpital Saint-Louis, Virologie, Paris, France.
authors.forename: Félix
authors.initials: F
authors.lastname: Agbalika
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Université Paris 06, INSERM, Centre d'Immunologie et des Maladies Infectieuses, Unité Mixte de Recherche (UMR) 1135, Équipes de Recherche Labellisées Centre National de la Recherche Scientifique (CNRS) 8255, Paris, France.|Département d'Immunologie, CHU Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Autran
authors.affiliation: Hôpital Saint-Louis, Immunologie Clinique, Equipe d'Accueil 3518, Université Paris Diderot Paris 7, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Oksenhendler
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Université Paris 06, INSERM, Centre d'Immunologie et des Maladies Infectieuses, Unité Mixte de Recherche (UMR) 1135, Équipes de Recherche Labellisées Centre National de la Recherche Scientifique (CNRS) 8255, Paris, France.|Département d'Immunologie, CHU Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France.
authors.forename: Guislaine
authors.initials: G
authors.lastname: Carcelain
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D055610:Antigens, CD1d / Q000032:analysis; D016175:B-Lymphocyte Subsets / Q000473:pathology* / Q000821:virology; D005871:Castleman Disease / Q000473:pathology* / Q000821:virology*; D049109:Cell Proliferation; D005260:Female; D019288:Herpesvirus 8, Human / Q000302:isolation & purification*; D006801:Humans; D007072:Immunoglobulin D / Q000032:analysis; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000473:pathology* / Q000821:virology; D012514:Sarcoma, Kaposi / Q000473:pathology / Q000821:virology; D013154:Spleen / Q000473:pathology / Q000821:virology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis
chemical_list: D055610:Antigens, CD1d; D007072:Immunoglobulin D; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7