CD4/CD8 Antibodies Reduce Histopathological Damage in Salivary Glands of Spontaneously Diabetic Mice

Abstract

Background and aims:Diabetes affects the metabolism promoting damage in different tissues, including salivary glands. Current treatments, such as insulin, are ineffective to recovery of these tissues. In this aspect, the immunotherapy has been tested, but it can be inefficient as an agent for the control of damage caused by diabetes. The aim of this study to evaluate the association in anti-CD4 and anti-CD8 monoclonal antibody in the recovery of salivary glands of diabetic NOD mice. Material and methods: Fifteen spontaneously diabetic mice (NOD) were divided into three groups with 5 animals each: group I (Balb/C control mice), group II (untreated NOD mice), group III (NOD mice treated with CD4 and CD8 antibodies). The CD4 and CD8 antibodies (IMUNY, Rheabiotech Ltda, Brazil) were administered by intravenously injections (25 ug/days: 0, 7, 14, and 21). After treatment salivary glands samples were analyzed by immunofluorescence, microscopy, light microscopy and stereology. (ethical approval process: 304/11), Analysis of variance (ANOVA) and Kruskal-Wallis nonparametric test were used. Results: Elevated levels of glucose (mg/dl) were observed in untreated animals (group II) (605.25 ± 31.23, p≤0.05), whereas in treated animals (group III), were noted a decrease in these levels (464.77 ± 39.66, p≤0.05). Tissue restructure, characterized by cell volume recovery, also was observed in group III (nuclear volume of parotid glands: (109.91 ± 02.03, p≤0.05) and submandibular glands: (107.52 ± 02, p≤0.05) (cytoplasmic volume of parotid glands: (356.14 ± 26.34, p≤0.05) and submandibular glands: (331.22 ± 32.11, p≤0.05). Intense signaling (+++) of insulin receptors was observed in animals of group I. On the other hand, in group II was noted a reduction of these receptors (+). In treated animals (group III) were observed a recovery of the insulin receptors (+++). Conclusions: This treatment was effective in the recovery of salivary acinar cells, contributed also to homeostasis of body metabolism. Thus, this immunomodulation promoted a beneficial effect on the recovery of these tissues. key words: anti CD4 and CD8, immunotherapy, salivary glands, diabetes mellitus 157 25. Robinson CP. Elevated levels of cysteine protease activity in saliva and salivary glands of the nonobese diabetic (NOD) mouse model for Sjogren syndrome. Proc Natl Acad Sci 94 (11): 5767-71, 1997 26. Wildenberg ME, Van Helden-Meeuwsen CG, van de Merwe JP, Moreno C, Drexhage HA, Versnel MA. Lack of CCR5 on dendritic cells promotes a proinflammatory environment in submandibular glands of the NOD mouse. J Leukoc Biol 83(5): 1194-200, 2008 27. Markopoulos AK, Belazi M. Histopathological and immunohistochemical features of the labial salivary glands in children with type I diabetes. 29. Parish N, Cooke A. Characterisation of CD8 monoclonal antibody-induced protection from diabetes in NOD mice. Autoimmunity 38(8): 597-604, 2005 30. Yagi H, Matsumoto M, Kunimoto K, Kawaguchi J, Makino S, Harada M. Analysis of the roles of CD4+ and CD8+ T cells in autoimmune diabetes...

Effect of antioxidant treatment with n-acetylcysteine and swimming on lipid expression of sebaceous glands in diabetic mice

“…Mice from the DNa group received a daily intraperitoneal dose of 50 mg/kg NAC and a weekly intravenous dose of 25 µl anti-CD4 and anti-CD8 antibodies, to block the negative effects of NAC (mainly the lymphocyte stimulation) for 21 days. Previous group studies showed a reduction in lymphocyte activity in pancreatic beta cells submitted to treatment with anti-CD4 and anti-CD8, in the same interventions described in this work 23 , 24 . In animals from the DS-Na group, both treatments from the DS and DNa groups were applied.…”

“…NAC is a potent antioxidant due to its capacity to stimulate the synthesis of GSH 22 , the enzyme responsible for the antioxidant defense system 25 . However, NAC can increase the infiltration of CD4 and CD8 T lymphocytes in the pancreas, causing the destruction of beta cells and consequently aggravating the effects of diabetes on tissues 23 , 24 .…”