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International Immunology Advance Access published online on April 19, 2007
International Immunology, doi:10.1093/intimm/dxm028
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© The Japanese Society for Immunology. 2007. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Requirements for CD4+ T cell levels in acute Mycobacterium bovis strain bacille Calmette Guérin (BCG)-induced granulomas differ for optimal mycobacterial control versus granuloma formation

Laura H. Hogan, Erika Heninger, Rebecca A. Elsner, Heidi A. Vonderheid, Paul Hulseberg, Dominic Co and Matyas Sandor

Correspondence to: Correspondence to: M. Sandor; E-mail: msandor{at}wisc.edu

Bacille Calmette Guérin (BCG)-induced granulomas contain T cells that express a broad TCR repertoire even at the level of the individual lesion. We have developed a BCG infection model in mice having only one T cell specific for a recombinant BCG epitope expressed in a lipoprotein fusion protein. Here we report that the single T cell model induces well-formed granulomas, but has weaker protection than that conferred by wild-type granulomas. This finding correlates with lower CD4+ T cell recruitment into acute granulomas (3 weeks post infection). Chronic granulomas (6 weeks post infection) contain similar proportions of CD4+ T cells in both models, but in the single T cell model the proportion of leukocyte function-associated antigen-1 low, non-IFN{gamma}-producing CD4+ T cells is lower. In fact, even though it is likely that there are very few, if any, IFN{gamma}+ CD4+ T cells present in the single T cell model, granuloma integrity is not influenced, indicating that high levels of IFN{gamma} are not required for granuloma maintenance. These data underline the importance of early CD4+ T cell recruitment into the granuloma to anti-mycobacterial protection and show that CD4+ T cell levels required for granuloma formation and optimal protection are different. These data also show that T cell repertoire complexity contributes to protection against mycobacteria.

Keywords: inflammation, mycobacterium, T cell receptor

Transmitting editor: A. Falus

Received 20 December 2006, accepted 22 February 2007.


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