iNKT and memory B-cell alterations in HHV-8 multicentric Castleman disease

• Published in: Blood Vol. 129; no. 7; pp. 855 - 865
• Main Authors: Sbihi, Zineb, Dossier, Antoine, Boutboul, David, Galicier, Lionel, Parizot, Christophe, Emarre, Amandine, Hoareau, Bénédicte, Dupin, Nicolas, Marcelin, Anne-Geneviève, Oudin, Anne, Fieschi, Claire, Agbalika, Félix, Autran, Brigitte, Oksenhendler, Eric, Carcelain, Guislaine
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.02.2017; American Society of Hematology
• Subjects: Adult; Aged; Aged, 80 and over; Antigens, CD1d - analysis; B-Lymphocyte Subsets - pathology; B-Lymphocyte Subsets - virology; Biochemistry, Molecular Biology; Castleman Disease - pathology; Castleman Disease - virology; Cell Proliferation; Female; Genomics; Herpesvirus 8, Human - isolation & purification; Humans; Immunoglobulin D - analysis; Life Sciences; Male; Middle Aged; Natural Killer T-Cells - pathology; Natural Killer T-Cells - virology; Sarcoma, Kaposi - pathology; Sarcoma, Kaposi - virology; Spleen - pathology; Spleen - virology; Tumor Necrosis Factor Receptor Superfamily, Member 7 - analysis
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2016-06-719716

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. •HHV-8 MCD is associated with a decrease of iNKT and memory B cells.•iNKT decrease contributes to B-cell abnormalities in coculture experiments.