HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Forbes, E. K. Articles by Tchilian, E. Z. Search for Related Content PubMed PubMed Citation Articles by Forbes, E. K. Articles by Tchilian, E. Z. Pubmed/NCBI databases Substance via MeSH

Multifunctional, High-Level Cytokine-Producing Th1 Cells in the Lung, but Not Spleen, Correlate with Protection against Mycobacterium tuberculosis Aerosol Challenge in Mice

The Jenner Institute, University of Oxford, Headington, Oxford, United Kingdom

Boosting bacillus Calmette-Guérin (BCG)-primed mice with a recombinant adenovirus expressing Mycobacterium tuberculosis Ag 85A by different administration 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 Ag 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 Ag 85A and an increased response to purified protein derivative. This effect is associated with the presence in the lung of multifunctional T cells, with high median fluorescence intensity and integrated median fluorescence intensity for IFN-, IL-2, and TNF. In contrast, mice immunized with BCG alone have few Ag-specific cells in the lung and a low proportion of multifunctional cells, although individual cells have high median fluorescence intensity. Successful immunization regimes appear to induce Ag-specific cells with abundant intracellular cytokine staining.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Address correspondence and reprint requests to Dr. Elma Tchilian, The Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Headington, Oxford OX3 7DQ, U.K. E-mail address: elma.tchilian{at}ndm.ox.ac.uk

² Abbreviations used in this paper: BCG, bacillus Calmette-Guérin; i.n., intranasal; i.d., intradermal; MFI, median fluorescence intensity; PPD, purified protein derivative.

This article has been cited by other articles:

				E. Z. Tchilian, C. Desel, E. K. Forbes, S. Bandermann, C. R. Sander, A. V. S. Hill, H. McShane, and S. H. E. Kaufmann Immunogenicity and Protective Efficacy of Prime-Boost Regimens with Recombinant {Delta}ureC hly+ Mycobacterium bovis BCG and Modified Vaccinia Virus Ankara Expressing M. tuberculosis Antigen 85A against Murine Tuberculosis Infect. Immun., February 1, 2009; 77(2): 622 - 631. [Abstract] [Full Text] [PDF]