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Assessing the role of galectin-1 in the migration of effector CD8+ T lymphocytes and their interaction with antigen presenting cells

Grant number: 12/12615-7
Support Opportunities:Scholarships abroad - Research Internship - Doctorate (Direct)
Effective date (Start): October 01, 2012
Effective date (End): July 31, 2013
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:João Gustavo Pessini Amarante Mendes
Grantee:Tiago Clemente Machado
Supervisor: Sebastian Amigorena
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: Institut Curie, France  
Associated to the scholarship:11/07444-6 - New role for galectin-1 as effector molecule of cytotoxic cells, BP.DD

Abstract

Exocytosis of secretory granules is the main effector mechanism of CD8+ T cells (also known as cytotoxic T lymphocytes - CTLs) and is an important weapon against cancer and pathogen infected cells. Despite intense research on the development, activation and effector function of these cells, the understanding of molecular mechanisms involved in the directed target cell degranulation, and death of this cell and efector cell survival during the effector cytotoxic attack remains limited. Particularly, little is known about the composition / structure of the lytic granules of CTLs. The literature shows that perforin and certain granzymes are essential to induce death in target cells in vitro but in vivo is still controversial as the major inducers of this process. Previous results from our group identified by a proteomics analysis, a few tens of new proteins of these granules, and some components are known. Among them was identified galectin-1 (GAL-1), a lectin which recognizes beta-galactosides and participates in many biological processes, including the adaptive immune response. Galectins glucans can interact with cell surfaces in the cells of the immune system and thereby promote the modulation of the production of cytokines and mediators in cell adhesion, apoptosis, chemotaxis and endocytosis. The literature reports the action of GAL-1 by exogenous only through its secretion by an unconventional pathway that depends on keeping their carbohydrate binding region. Initial data from our group suggest a new scenario for this protein in the context of the response of effector cytotoxic cells, in which Gal-1 is present in cytotoxic granules, and thus could have a relationship with a role in the response of cytotoxic effector. Our preliminary results support this hypothesis, through the techniques of transmission electron microscopy and confocal laser scanning and in vivo cytotoxicity assays indicate the relationship of Gal-1 with the role of cytotoxic CTLs, since Gal-1KO animals there was a significantly greater number of target cells when compared to living with wildlife. We also show by ELISPOT technique that, in the deficiency of Gal-1 cells there is a significantly higher number of interferon gamma-producing CTLs in response to binding of the TCR and CD107a staining seen that there is greater degranulation in CTLs Gal -1KO. The evaluation of the effector response in the spleen of animals GAL1 ko, the profile of cytokines produced and if the absence of lectin alters the relationship between CTLs and antigen-presenting cells in the lymph nodes, will help us better understand the physiology of the CTLs and the role of GAL1 in its operation. (AU)

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