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  • Title: Requirements for CD4(+) T cell levels in acute Mycobacterium bovis strain bacille Calmette Guerin (BCG)-induced granulomas differ for optimal mycobacterial control versus granuloma formation.
    Author: Hogan LH, Heninger E, Elsner RA, Vonderheid HA, Hulseberg P, Co D, Sandor M.
    Journal: Int Immunol; 2007 May; 19(5):627-33. PubMed ID: 17446212.
    Abstract:
    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-IFNgamma-producing CD4(+) T cells is lower. In fact, even though it is likely that there are very few, if any, IFNgamma(+) CD4(+) T cells present in the single T cell model, granuloma integrity is not influenced, indicating that high levels of IFNgamma 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.
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