Characterization of Natural Killer and gamma-delta T cells in the immunotherapy of experimental tuberculosis with DNAhsp65 genetic vaccine.

• Grant number: 09/04544-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2009
• End date: July 31, 2011
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Celio Lopes Silva
• Grantee: Luana Silva Soares
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

In 1993, the World Health Organization (WHO) declared Tuberculosis (TB) as a global emergency due to its epidemical relevance and the need to improve its control. The number of cases is increasing in numerous countries and is becomingexacerbated for two reasons: the increasing numbers of multidrug-resistant (MDR)and extensively drug resistant (XDR) strains, partially due to the co-infection with HIV/AIDS. These reasons make necessary the development of more efficient vaccines and therapies for TB control. It is considered that for the development of these new prophylactic and therapeutic resources is necessary a detailedunderstanding of each component of the immunological response during TB.Furthermore, recent studies sustain that even new anti-TB drugs would be developed, the immunopathological lesions observed in lungs of TB patients will get better only with a concomitant modulation of the immune response. In this sense, The Centre for Tuberculosis Research from FMRP-USP works in a genetic vaccine withimmunotherapeutic properties which encodes the 65 kDa heat-shock protein of Mycobacterium leprae (DNAhsp65). Previous studies from our laboratorydemonstrated that the therapeutic effects of DNAhsp65 include the modulation of immune response to a Th1 pattern with participation of gamma-delta, CD8+ and CD4+ T lymphocytes. Other studies of our group suggest that natural killer cells (NK)also participate in this response. These data are in accordance with recent reportsthat emphasize the importance of the participation of cellular populations less well-studied in TB and that would mediate important processes against the bacillus. Thus,our objective is a comprehensive characterization of NK cells and GD T lymphocytes in DNAhsp65 immunotherapy of TB. For this purpose, these cell types will be studied in detail, with special attention to those present in tuberculous granuloma employing immunohistochemistry, laser-capture microdissection and Real Time PCR. This analysis will contribute to a better characterization of cellular populations less studied in TB and in the immunotherapy against TB, particularly those present at the local of bacilli concentration. The final goal of this strategy is the design of new and better vaccinesand immunotherapies.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SOARES, Luana Silva. Characterization of gamma-delta T cells and natural killer cells in the immunotherapy of experimental tuberculosis with DNAhsp65 genetic vaccine. 2011. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.