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 Google Scholar Articles by Ryan, A. A. Articles by Triccas, J. A. PubMed PubMed Citation Articles by Ryan, A. A. Articles by Triccas, J. A. Pubmed/NCBI databases Substance via MeSH

Antigen Load Governs the Differential Priming of CD8 T Cells in Response to the Bacille Calmette Guérin Vaccine or Mycobacterium tuberculosis Infection¹

Anthony A. Ryan^,*, Jonathan K. Nambiar^,*, Teresa M. Wozniak, Ben Roediger, Elena Shklovskaya, Warwick J. Britton^,, Barbara Fazekas de St. Groth and James A. Triccas^2,,*

^* Microbial Pathogenesis and Immunity Group, Discipline of Infectious Diseases, Centenary Institute of Cancer Medicine and Cell Biology, and Discipline of Medicine, University of Sydney, Australia

One reason proposed for the failure of Mycobacterium bovis bacille Calmette Guérin (BCG) vaccination to adequately control the spread of tuberculosis is a limited ability of the vaccine to induce effective CD8 T cell responses. However, the relative capacity of the BCG vaccine and virulent Mycobacterium tuberculosis to induce activation of CD8 T cells, and the factors that govern the initial priming of these cells after mycobacterial infection, are poorly characterized. Using a TCR transgenic CD8 T cell transfer model, we demonstrate significant activation of Ag-specific CD8 T cells by BCG, but responses were delayed and of reduced magnitude compared with those following infection with M. tuberculosis. The degree of CD8 T cell activation was critically dependent on the level of antigenic stimulation, as modifying the infectious dose to achieve comparable numbers of BCG or M. tuberculosis in draining lymph nodes led to the same pattern of CD8 T cell responses to both strains. Factors specific to M. tuberculosis infection did not influence the priming of CD8 T cells, as codelivery of M. tuberculosis with BCG did not alter the magnitude of BCG-induced T cell activation. Following transfer to RAG-1^–/– recipients, BCG and M. tuberculosis-induced CD8 T cells conferred equivalent levels of protection against M. tuberculosis infection. These findings demonstrate that BCG is able to prime functional CD8 T cells, and suggest that effective delivery of Ag to sites of T cell activation by vaccines may be a key requirement for optimal CD8 T cell responses to control mycobacterial infection.

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 This work was supported by the National Health and Medical Research Council of Australia. J.A.T. is supported by an NHMRC Career Development Award, and B.F. de S.G. is supported by an NHMRC Principal Research Fellowship. A.A.R., B.R., and J.K.N. are supported by Australian Postgraduate Awards and T.M.W. is the recipient of the University of Sydney Faculty of Medicine Postgraduate Scholarship.

² Address correspondence and reprint requests to Dr. James A. Triccas, Discipline of Infectious Diseases and Immunology, University of Sydney, Sydney, Australia. E-mail address: jamiet{at}infdis.usyd.edu.au

³ Abbreviations used in this paper: DC, dendritic cell; BCG, M. bovis bacille Calmette Guérin; DLN, draining lymph node; RD1, region of deletion 1.