title: Long-term administration of IgG2a anti-NK1.1 monoclonal antibody ameliorates lupus-like disease in NZB/W mice in spite of an early worsening induced by an IgG2a-dependent BAFF/BLyS production.
abstract: The role of natural killer (NK) T cells in the development of lupus-like disease in mice is still controversial. We treated NZB/W mice with anti-NK1.1 monoclonal antibodies (mAbs) and our results revealed that administration of either an irrelevant immunoglobulin G2a (IgG2a) mAb or an IgG2a anti-NK1.1 mAb increased the production of anti-dsDNA antibodies in young NZB/W mice. However, the continuous administration of an anti-NK1.1 mAb protected aged NZB/W mice from glomerular injury, leading to prolonged survival and stabilization of the proteinuria. Conversely, the administration of the control IgG2a mAb led to an aggravation of the lupus-like disease. Augmented titres of anti-dsDNA in NZB/W mice, upon IgG2a administration, correlated with the production of BAFF/BLyS by dendritic, B and T cells. Treatment with an anti-NK1.1 mAb reduced the levels of interleukin-16, produced by T cells, in spleen cell culture supernatants from aged NZB/W. Adoptive transfer of NK T cells from aged to young NZB/W accelerated the production of anti-dsDNA in recipient NZB/W mice, suggesting that NK T cells from aged NZB/W are endowed with a B-cell helper activity. In vitro studies, using purified NK T cells from aged NZB/W, showed that these cells provided helper B-cell activity for the production of anti-dsDNA. We concluded that NK T cells are involved in the progression of lupus-like disease in mature NZB/W mice and that immunoglobulin of the IgG2a isotype has an enhancing effect on antibody synthesis due to the induction of BAFF/BLyS, and therefore have a deleterious effect in the NZB/W mouse physiology.
authors.affiliation: Immunology Laboratory, Heart Institute (INCOR), University of São Paulo, São Paulo, Brazil.
authors.forename: Edilberto
authors.initials: E
authors.lastname: Postól
authors.forename: André
authors.initials: A
authors.lastname: Meyer
authors.forename: Fabíola
authors.initials: F
authors.lastname: Cardillo
authors.forename: Raquel
authors.initials: R
authors.lastname: de Alencar
authors.forename: Daniel
authors.initials: D
authors.lastname: Pessina
authors.forename: Jorge
authors.initials: J
authors.lastname: Nihei
authors.forename: Mário
authors.initials: M
authors.lastname: Mariano
authors.forename: José
authors.initials: J
authors.lastname: Mengel
mesh_terms: D000375:Aging / Q000276:immunology; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000950:Antigens, Ly / Q000276:immunology; D053264:B-Cell Activating Factor / Q000096:biosynthesis*; D002478:Cells, Cultured; D018450:Disease Progression; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology / Q000627:therapeutic use*; D019410:Interleukin-16 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology / Q000637:transplantation; D008070:Lipopolysaccharides / Q000276:immunology; D008099:Liver / Q000276:immunology; D008181:Lupus Nephritis / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008815:Mice, Inbred Strains; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000276:immunology; D012720:Severity of Illness Index; D013154:Spleen / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D053264:B-Cell Activating Factor; D007074:Immunoglobulin G; D019410:Interleukin-16; C527211:Klrb1c protein, mouse; D008070:Lipopolysaccharides; D055651:NK Cell Lectin-Like Receptor Subfamily B; C505720:Tnfsf13b protein, mouse