Mycobacterium bovis strain bacillus Calmette-Guerin-induced liver granulomas contain a diverse TCR repertoire, but a monoclonal T cell population is sufficient for …

LH Hogan, K Macvilay, B Barger, D Co… - The Journal of …, 2001 - journals.aai.org
LH Hogan, K Macvilay, B Barger, D Co, I Malkovska, G Fennelly, M Sandor
The Journal of Immunology, 2001journals.aai.org
Granuloma formation is a form of delayed-type hypersensitivity requiring CD4+ T cells.
Granulomas control the growth and dissemination of pathogens, preventing host
inflammation from harming surrounding tissues. Using a murine model of Mycobacterium
bovis strain bacillus Calmette-Guérin (BCG) infection we studied the extent of T cell
heterogeneity present in liver granulomas. We demonstrate that the TCR repertoire of
granuloma-infiltrating T cells is very diverse even at the single-granuloma level, suggesting …
Abstract
Granuloma formation is a form of delayed-type hypersensitivity requiring CD4+ T cells. Granulomas control the growth and dissemination of pathogens, preventing host inflammation from harming surrounding tissues. Using a murine model of Mycobacterium bovis strain bacillus Calmette-Guérin (BCG) infection we studied the extent of T cell heterogeneity present in liver granulomas. We demonstrate that the TCR repertoire of granuloma-infiltrating T cells is very diverse even at the single-granuloma level, suggesting that before granuloma closure, a large number of different T cells are recruited to the lesion. At the same time, the TCR repertoire is selected, because AND TCR transgenic T cells (Vα11/Vβ3 anti-pigeon cytochrome c) are preferentially excluded from granulomas of BCG-infected AND mice, and cells expressing secondary endemic Vβ-chains are enriched among AND cells homing to granulomas. Next, we addressed whether TCR heterogeneity is required for effective granuloma formation. We infected 5CC7/recombinase-activating gene 2−/− mice with recombinant BCG that express pigeon cytochrome c peptide in a mycobacterial 19-kDa bacterial surface lipoprotein. A CD4+ T cell with a single specificity in the absence of CD8+ T cells is sufficient to form granulomas and adequately control bacteria. Our study shows that expanded monoclonal T cell populations can be protective in mycobacterial infection.
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