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. J Immunol 2001 May 15;166(10):6367-75
Date
05/09/2001Pubmed ID
11342661DOI
10.4049/jimmunol.166.10.6367Scopus ID
2-s2.0-0035873655 (requires institutional sign-in at Scopus site) 32 CitationsAbstract
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.
Author List
Hogan LH, Macvilay K, Barger B, Co D, Malkovska I, Fennelly G, Sandor MAuthor
Brittany Player DO Assistant Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Movement
Clone Cells
Epitopes, T-Lymphocyte
Granuloma
Immunophenotyping
Liver
Lymphocyte Activation
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Transgenic
Mycobacterium Infections
Mycobacterium bovis
Receptors, Antigen, T-Cell
Spleen
T-Lymphocyte Subsets
