Trogocytosis role in the expression of CD80 and CD86 molecules on activated CD4+ t cells from mice neonates

• Grant number: 13/07272-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2013
• End date: December 31, 2013
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Cyro Alves de Brito
• Grantee: Jana Trancoso dos Santos
• Host Institution: Instituto Adolfo Lutz (IAL). Coordenadoria de Controle de Doenças (CCD). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Several peculiarities differentiate the newborn and the adult immune systems. Many characteristics of the neonate immune systems, usually, result on negative modulation of inflammatory response, avoiding exacerbated responses against many non-infectious antigens, which they are exposed in this period. In the other hand, the incapability of the immune system to generate strong responses is related to a greater susceptibility to development of bacterial and viral infections in infants. The deficiency of the neonate response to T-dependent antigens may be resulted from many reasons, like the lack of an appropriated anatomic microenvironment for T-B cells interaction, through the low expression of co-stimulatory and Major Histocompatibility Complex (MHC) molecules and high expression of suppressing molecules. After antigenic stimulation, comparing to adults, our previous results show an increased expression of CD80 and CD86 molecules on newborn mice CD4+ T cells. The CD80/CD86-CTLA-4 interaction in T-T activation models has been considered and important mechanism to suppress the proliferation and survival of activated T lymphocytes. These evidences suggest that expression of CD80 and CD86 molecules on T lymphocytes may be related to a low immune response and to predisposition to tolerance seeing on neonate. The trogocytosis, the intercellular transfer of membrane-bound proteins from one APC to a T lymphocyte, is a probably mechanism responsible for CD80 and CD86 expression on T lymphocytes. This requires a cell-cell contact, it occurs on different populations, like T and B lymphocytes and NK cells and allows the transfer of intact proteins from one cell to another. The trogocytosis plays a role not only in the negative regulation of immune response , but also, as a mechanism of tumor escape and viral infections progression, by the transfer of suppressing molecules or viral receptors, respectively. The aim of this project is to study the role of trogocytosis on CD80 and CD86 expression on neonate T lymphocytes. All acknowledge about mechanisms involved in the expression of co-stimulatory molecules on neonate T lymphocytes will help to develop new analysis, vaccinal and immunomodulatory protocols in neonates and also to clarify the aspects involved on newborn susceptibility to infections. (AU)