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

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

Autor Postol, Edilberto Google Scholar
Meyer, Andre Google Scholar
Cardillo, Fabiola Google Scholar
Alencar, Raquel de Google Scholar
Pessina, Daniel Google Scholar
Nihei, Jorge Google Scholar
Mariano, Mario Autor UNIFESP Google Scholar
Mengel, Jose Google Scholar
Instituição Fiocruz MS
Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Resumo 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.
Palavra-chave BAFF/BLyS
Fc receptor
interleukin-16
natural killer T cells
systemic lupus erythematosus
Toll-like receptor
Idioma Inglês
Financiador Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Número do financiamento CNPq: 305835/2003-3
FAPESP: 95/9379-2
FAPESP: 97/06225-0
Data de publicação 2008-10-01
Publicado em Immunology. Malden: Wiley-Blackwell, v. 125, n. 2, p. 184-196, 2008.
ISSN 0019-2805 (Sherpa/Romeo, fator de impacto)
Publicador Wiley-Blackwell
Extensão 184-196
Fonte http://dx.doi.org/10.1111/j.1365-2567.2008.02835.x
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000258972400006
Endereço permanente http://repositorio.unifesp.br/handle/11600/30917

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