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Protection conferred by heterologous vaccination against tuberculosis is dependent on the ratio of CD 4 + / CD 4 + F oxp3 + cells
Author(s) -
Fedatto Paola Fernanda,
Sérgio Cássia Alves,
Paula Marina Oliveira e,
Gembre Ana Flávia,
Franco Luís Henrique,
Wowk Pryscilla Fanini,
Ramos Simone Gusmão,
Horn Cynthia,
Marchal Gilles,
Turato Walter Miguel,
Silva Célio Lopes,
Fonseca Denise Morais,
Bonato Vânia Luiza Deperon
Publication year - 2012
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12006
Subject(s) - heterologous , dna vaccination , spleen , biology , tuberculosis vaccines , microbiology and biotechnology , immunization , bcg vaccine , vaccination , virology , immunology , immune system , tuberculosis , mycobacterium tuberculosis , medicine , biochemistry , gene , pathology
Summary CD 4 + F oxp3 + regulatory T cells inhibit the production of interferon‐γ, which is the major mediator of protection against M ycobacterium tuberculosis infection. In this study, we evaluated whether the protection conferred by three different vaccines against tuberculosis was associated with the number of spleen and lung regulatory T cells. We observed that after homologous immunization with the 65 000 molecular weight heat‐shock protein (hsp 65) DNA vaccine, there was a significantly higher number of spleen CD 4 + F oxp3 + cells compared with non‐immunized mice. Heterologous immunization using bacillus Calmette–Guérin ( BCG ) to prime and DNA ‐ hsp 65 to boost ( BCG / DNA ‐ hsp 65) or BCG to prime and culture filtrate proteins ( CFP )‐ C p G to boost ( BCG / CFP ‐ C p G ) induced a significantly higher ratio of spleen CD 4 + / CD 4 + F oxp3 + cells compared with non‐immunized mice. In addition, the protection conferred by either the BCG / DNA ‐ hsp 65 or the BCG / CFP ‐ C p G vaccines was significant compared with the DNA ‐ hsp 65 vaccine. Despite the higher ratio of spleen CD 4 + / CD 4 + F oxp3 + cells found in BCG / DNA ‐ hsp 65‐immunized or BCG / CFP ‐ C p G ‐immunized mice, the lungs of both groups of mice were better preserved than those of DNA ‐ hsp 65‐immunized mice. These results confirm the protective efficacy of BCG / DNA ‐ hsp 65 and BCG / CFP ‐ C p G heterologous prime‐boost vaccines and the DNA ‐ hsp 65 homologous vaccine. Additionally, the prime‐boost regimens assayed here represent a promising strategy for the development of new vaccines to protect against tuberculosis because they probably induce a proper ratio of CD 4 + and regulatory ( CD 4 + F oxp3 + ) cells during the immunization regimen. In this study, this ratio was associated with a reduced number of regulatory cells and no injury to the lungs.