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*
Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, Madison, WI 53706; and
Department of Pediatrics, Jacobi Medical Center and Albert Einstein College of Medicine, Brooklyn, NY 10461
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 (V
11/V
3 anti-pigeon cytochrome c) are
preferentially excluded from granulomas of BCG-infected AND mice, and
cells expressing secondary endemic V-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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