Multifunctional, high-level cytokine-producing Th1 cells in the lung, but not spleen, correlate with protection against Mycobacterium tuberculosis aerosol challenge in mice.

Multifunctional, high-level cytokine-producing Th1 cells in the lung, but not spleen, correlate with protection against Mycobacterium tuberculosis aerosol challenge in mice.
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DOI:
10.4049/jimmunol.181.7.4955
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发表时间:
2008-10-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Tchilian EZ
Tchilian EZ
中科院分区:
其他
文献类型:
--
作者:
Forbes EK;Sander C;Ronan EO;McShane H;Hill AV;Beverley PC;Tchilian EZ

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Boosting BCG-primed mice with a recombinant adenovirus expressing M. tuberculosis antigen 85A by different routes has very different effects on protection against aerosol challenge with M. tuberculosis. Mice boosted intradermally make very strong splenic CD4 and CD8 Th1 cytokine responses to antigen 85A, but show no change in lung mycobacterial burden over BCG primed animals. In contrast intranasally boosted mice show greatly reduced mycobacterial burden and make a much weaker splenic response but a very strong lung CD4 and CD8 response to antigen 85A and an increased response to PPD. This is associated with the presence in the lung of multifunctional T cells, with high median fluorescence intensities and integrated median fluorescence intensities for IFNγ, IL-2 and TNF. In contrast, mice immunized with BCG alone have few antigen-specific cells in the lung and a low proportion of multi-functional cells although individual cells have high median fluorescence intensities. Successful immunization regimes appear to induce antigen-specific cells with abundant intracellular cytokine staining.
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