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The activation of dendritic cells by ArtinM favors cross-priming of CD8+ T cells by antigens of pathogens?

Grant number: 10/01171-5
Support type:Scholarships in Brazil - Master
Effective date (Start): September 01, 2010
Effective date (End): February 29, 2012
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal researcher:Maria Cristina Roque Antunes Barreira
Grantee:Thiago Aparecido da Silva
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The lectin ArtinM obtained from crude extract of seeds of jackfruit, Artocarpus integrifolia, is specific to manotriose Man alpha 1-3 [Man alpha 1-6] Man, and endowed with important immunomodulatory property, held by the induction of APCs to produce IL-12. As a result, administration of the lectin to mice is followed by secretion of IFN-gamma by lymphocytes and establishment of a pattern of immune response of Th1 type, capable of conferring protection against intracellular pathogens, as seen in infections with Leishmania major, Leishmania amazonensis and Paracoccidioides brasiliensis. The development of effector function of CD8+ T cells is crucial in the face of several bacterial and viral infections. The activation of these cells occurs through the molecule MHC class I, classical pathway of antigen presentation, but when this molecule is involved in the presentation of antigens internalized by APCs, has been the route of cross-presentation. This process results in cross-priming of CD8+ T cells, contributing to the protection against pathogens that require the participation of CD8+ T cells as effector cells of immunity. Dendritic cells are professional APCs key role in cross-presentation. For this to happen requires the participation of mature dendritic cells, through its membrane receptors, costimulatory molecules and cytokines secreted. This paper aims to analyze the impact of the Th1 cytokines produced by dendritic cells under stimulation ArtinM in cross-presentation of antigens, by checking the encouragement of cross-priming of CD8+ lymphocytes. As research strategy, we propose the administration of the lectin to mice, followed by inoculation of a glycosylated antigen (albumin chicken egg, OVA). The CD8alpha+ dendritic cells and CD8+ T cells derived from the spleen of these animals will be purified and co-cultured in the presence of OVA. The population of CD8+ T cells will be analyzed by FACS, identifying the proportion of marked intracellular cytokine IFN-gamma. Be also performed cytotoxicity assays, cell proliferation assays and measurement of IL-2 and IFN-gamma. There will be a comparative analysis of these parameters between mice which have been administered, or not, ArtinM.Key words: ArtinM, CD8 + T cells, dendritic cells, cross-priming.

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