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

Granuloma formation is a form of delayed-type hypersensitivity requiring CD 4(+) T cells. Granulomas control the growth and dissemination of pathogens, preventing host inflammation from harming surrounding tissues. Using a mur ine model of Mycobacterium bovis strain bacillus Calmette-Guerin (BCG) infe ction we studied the extent of T cell heterogeneity present in liver granul omas. We demonstrate that the TCR repertoire of granuloma-infiltrating T ce lls is very diverse even at the single-granuloma level, suggesting that bef ore 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 (V alpha 11/V beta3 anti-pigeon cytochrome c) are pr eferentially excluded from granulomas of BCG-infected AND mice, and cells e xpressing secondary endemic V beta -chains are enriched among AND cells hom ing 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 pep tide in a mycobacterial 19-kDa bacterial surface lipoprotein. A CD4(+) T ce ll with a single specificity in the absence of CD8(+) T cells is sufficient to form granulomas and adequately control bacteria. Our study shows that e xpanded monoclonal T cell populations can be protective in mycobacterial in fection.