Evaluation of the cytotoxic profile of CD4+ t lymphocytes in the NOD mice diabetes model

• Grant number: 16/17115-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2016
• End date: October 31, 2018
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alessandro dos Santos Farias
• Grantee: Maurílio Bonora Junior
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Type 1 diabete (DM1A) is one of the most common diseases of the childhood and of the adolescence. There is a heterogeneity in its clinical expression, depending on the extension of the destruction of the ß pancreatic cells by the autoreactive T lymphocytes. Due to the difficult to assess human Langerhans islets in vivo, most of knowledge regarding this human disorder were acquired through studies made with the its experimental models, specially the Non Obese Diabetic mice (NOD mice). In this model, the clinical diabetes is developed similarly to the human disease, preceded by an pre-diabetes fase, which is characterized by the progressive infiltration of lymphocytes into the pancreatic islets (process called insulitis). It is known that the CD4 T cells are the primary population to invade the islets, followed by a posterior migration of CD8 T lymphocytes. This suggests the cytotoxic molecules, such as granzymes and perforins are important for the development of lesions at the ß pancreatic cells. Nevertheless, it is still to be clarified how CD4 T cells would be able to cause the first damages to the islets, since it effector functions are, at least traditionally, described as helper functions. Many studies have revealed that CD4 T cells are able to acquire a cytotoxic profile under special circumstances, like some bacterial and/or viral infections. Results of our group have shown that these CD4 T cells in fact acquire a cytotoxic activity in the models EAE and EAN, which are one CD4 T cells-mediated tissue-specific autoimmunity as well. Thus, with this project, we aim to investigate the importance of the cytotoxic mechanisms that the CD4 T lymphocytes may acquire during the development of the diabetes in NOD mice.