title: Mycobacterium bovis strain bacillus Calmette-Guérin-induced liver granulomas contain a diverse TCR repertoire, but a monoclonal T cell population is sufficient for protective granuloma formation.
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 (Valpha11/Vbeta3 anti-pigeon cytochrome c) are preferentially excluded from granulomas of BCG-infected AND mice, and cells expressing secondary endemic Vbeta-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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, Madison, WI 53706, USA.
authors.forename: L H
authors.initials: LH
authors.lastname: Hogan
authors.forename: K
authors.initials: K
authors.lastname: Macvilay
authors.forename: B
authors.initials: B
authors.lastname: Barger
authors.forename: D
authors.initials: D
authors.lastname: Co
authors.forename: I
authors.initials: I
authors.lastname: Malkovska
authors.forename: G
authors.initials: G
authors.lastname: Fennelly
authors.forename: M
authors.initials: M
authors.lastname: Sandor
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000502:physiology; D006099:Granuloma / Q000235:genetics / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D016130:Immunophenotyping; D008099:Liver / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009164:Mycobacterium Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D009163:Mycobacterium bovis / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis* / Q000235:genetics; D013154:Spleen / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D018984:Epitopes, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell