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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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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Author(s):
Postol, Edilberto [1] ; Meyer, Andre ; Cardillo, Fabiola [2] ; de Alencar, Raquel [1] ; Pessina, Daniel [2] ; Nihei, Jorge [2] ; Mariano, Mario [3] ; Mengel, Jose [2]
Total Authors: 8
Affiliation:
[1] Univ Sao Paulo, Inst Heart INCOR, Immunol Lab, Sao Paulo - Brazil
[2] Fiocruz MS, Oswaldo Cruz Fdn, IGM, BR-40296710 Salvador, BA - Brazil
[3] Univ Fed Sao Paulo, Discipline Immunol, Dept Microbiol Immunol & Parasitol, Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: IMMUNOLOGY; v. 125, n. 2, p. 184-196, OCT 2008.
Web of Science Citations: 11
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. (AU)