RESUMEN
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.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Factor Activador de Células B/biosíntesis , Inmunoglobulina G/uso terapéutico , Nefritis Lúpica/prevención & control , Envejecimiento/inmunología , Animales , Anticuerpos Antinucleares/biosíntesis , Anticuerpos Monoclonales/inmunología , Antígenos Ly/inmunología , Células Cultivadas , Progresión de la Enfermedad , Femenino , Inmunoglobulina G/inmunología , Interleucina-16/biosíntesis , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/trasplante , Lipopolisacáridos/inmunología , Hígado/inmunología , Nefritis Lúpica/inmunología , Ratones , Ratones Endogámicos , Subfamilia B de Receptores Similares a Lectina de Células NK/inmunología , Índice de Severidad de la Enfermedad , Bazo/inmunología , Linfocitos T Colaboradores-Inductores/inmunologíaRESUMEN
Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels were evaluated in lipopolysaccharide (LPS)-stimulated cell cultured monocytes obtained from 24 type 1 and type 2 diabetic patients presenting inadequate (IN) or adequate (AD) metabolic control, and in 21 healthy individuals paired to patients for sex and age. The TNF-alpha levels in stimulated cultures of diabetic patients were similar to healthy individuals, and type 1 diabetic patients showed increased IL-6 supernatant levels. The tendency toward increased TNF-alpha and IL-6 levels was observed with metabolic control of type 1 and type 2 diabetic patients, suggesting that the control of diabetes improves the capacity of activation and maintenance of the proinflammatory immune response.