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International Immunology Advance Access originally published online on April 19, 2007
International Immunology 2007 19(5):627-633; 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

University of Wisconsin School of Medicine and Public Health, Pathology and Laboratory Medicine, 5468 Medical Science Center, 1300 University Avenue, Madison, WI 53705, USA

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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