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

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dc.contributor.authorPostol, Edilberto
dc.contributor.authorMeyer, Andre
dc.contributor.authorCardillo, Fabiola
dc.contributor.authorAlencar, Raquel de
dc.contributor.authorPessina, Daniel
dc.contributor.authorNihei, Jorge
dc.contributor.authorMariano, Mario [UNIFESP]
dc.contributor.authorMengel, Jose
dc.contributor.institutionFiocruz MS
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T13:51:42Z
dc.date.available2016-01-24T13:51:42Z
dc.date.issued2008-10-01
dc.description.abstractThe 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.en
dc.description.affiliationFiocruz MS, Oswaldo Cruz Fdn, IGM, BR-40296710 Salvador, BA, Brazil
dc.description.affiliationUniv São Paulo, Inst Heart INCOR, Immunol Lab, São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Discipline Immunol, Dept Microbiol Immunol & Parasitol, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Discipline Immunol, Dept Microbiol Immunol & Parasitol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIDCNPq: 305835/2003-3
dc.description.sponsorshipIDFAPESP: 95/9379-2
dc.description.sponsorshipIDFAPESP: 97/06225-0
dc.format.extent184-196
dc.identifierhttp://dx.doi.org/10.1111/j.1365-2567.2008.02835.x
dc.identifier.citationImmunology. Malden: Wiley-Blackwell, v. 125, n. 2, p. 184-196, 2008.
dc.identifier.doi10.1111/j.1365-2567.2008.02835.x
dc.identifier.issn0019-2805
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/30917
dc.identifier.wosWOS:000258972400006
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofImmunology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.subjectBAFF/BLySen
dc.subjectFc receptoren
dc.subjectinterleukin-16en
dc.subjectnatural killer T cellsen
dc.subjectsystemic lupus erythematosusen
dc.subjectToll-like receptoren
dc.titleLong-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 productionen
dc.typeinfo:eu-repo/semantics/article
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