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  • 1 Department of Pathology and Laboratory Medicine, University of Wisconsin, School of Medicine and Public Health, Madison, WI, 53706, USA
  • 2 Cellular and Molecular Pathology Training Program, University of Wisconsin, Madison, USA
  • 3 Microbiology Doctoral Training Program, University of Wisconsin, Madison, USA
  • 4 5468 MSC, 1300 University Ave, Madison, WI, 53705, USA
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Granulomas are the interface between host and mycobacteria, and are crucial for the surivival of both species. While macrophages are the main cellular component of these lesions, different lymphocyte subpopulations within the lesions also play important roles. Lymphocytes are continuously recruited into these inflammatory lesions via local vessels to replace cells that are either dying or leaving; however, their rate of replacement is not known. Using a model of granuloma transplantation and fluorescently labeled cellular compartments we report that, depending on the subpopulation, 10–80%, of cells in the granuloma are replaced within one week after transplantation. CD4+ T cells specific for Mycobacterium antigen entered transplanted granulomas at a higher frequency than Foxp3+ CD4+ T cells by one week. Interestingly, a small number of T lymphocytes migrated out of the granuloma to secondary lymphoid organs. The mechanisms that define the differences in recruitment and efflux behind each subpopulation requires further studies. Ultimately, a better understanding of lymphoid traffic may provide new ways to modulate, regulate, and treat granulomatous diseases.

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  • 1. T. Ulrichs S.H. Kaufmann 2006 New insights into the function of granulomas in human tuberculosis J Pathol 208 261269.

  • 2. D.O. Co 2004 Mycobacterial granulomas: keys to a long-lasting host-pathogen relationship Clin Immunol 113 130136.

  • 3. J.L. Flynn 1993 An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection J Exp Med 178 22492254.

    • Search Google Scholar
    • Export Citation
  • 4. H.E. Volkman 2004 Tuberculous granuloma formation is enhanced by a mycobacterium virulence determinant PLoS Biol 2 e367.

  • 5. H.A. Schreiber 2010 Dendritic cells in chronic mycobacterial granulomas restrict local anti-bacterial T cell response in a murine model PLoS One 5 e11453.

    • Search Google Scholar
    • Export Citation
  • 6. D.G. Russell 2007 Who puts the tubercle in tuberculosis? Nat Rev Microbiol 5 3947.

  • 7. C.L. Cosma O. Humbert L. Ramakrishnan 2004 Superinfecting mycobacteria home to established tuberculous granulomas Nat Immunol 5 828835.

    • Search Google Scholar
    • Export Citation
  • 8. C.L. Cosma 2008 Trafficking of superinfecting Mycobacterium organisms into established granulomas occurs in mammals and is independent of the Erp and ESX-1 mycobacterial virulence loci J Infect Dis 198 18511855.

    • Search Google Scholar
    • Export Citation
  • 9. J.G. Egen 2008 Macrophage and T cell dynamics during the development and disintegration of mycobacterial granulomas Immunity 28 271284.

    • Search Google Scholar
    • Export Citation
  • 10. D.O. Co 2006 Interactions between T cells responding to concurrent mycobacterial and influenza infections J Immunol 177 84568465.

    • Search Google Scholar
    • Export Citation
  • 11. L.H. Hogan 2007 Virally activated CD8 T cells home to Mycobacterium bovis BCG-induced granulomas but enhance antimycobacterial protection only in immunodeficient mice Infect Immun 75 11541166.

    • Search Google Scholar
    • Export Citation
  • 12. D.L. Sewell 2003 Infection withMycobacteriumbovis BCG diverts traffic of myelin oligodendroglial glycoprotein autoantigen-specific T cells away from the central nervous system and ameliorates experimental autoimmune encephalomyelitis Clin Diagn Lab Immunol 10 564572.

    • Search Google Scholar
    • Export Citation
  • 13. J.M. Davis L. Ramakrishnan 2008 “The very pulse of the machine”: the tuberculous granuloma in motion Immunity 28 146148.

  • 14. D.O. Co 2004 T cell contributions to the different phases of granuloma formation Immunol Lett 92 135142.

  • 15. S.H. Kaufmann C.H. Ladel 1994 Role of T cell subsets in immunity against intracellular bacteria: experimental infections of knockout mice with Listeria monocytogenes and Mycobacterium bovis BCG Immunobiology 191 509519.

    • Search Google Scholar
    • Export Citation
  • 16. C.H. Ladel 1995 Protective role of gamma/delta T cells and alpha/beta T cells in tuberculosis Eur J Immunol 25 28772881.

  • 17. T. Mogues 2001 The relative importance of T cell subsets in immunity and immunopathology of airborne Mycobacterium tuberculosis infection in mice J Exp Med 193 271280.

    • Search Google Scholar
    • Export Citation
  • 18. L.H. Hogan 2001 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 J Immunol 166 63676375.

    • Search Google Scholar
    • Export Citation
  • 19. J.L. Flynn 1992 Major histocompatibility complex class I-restricted T cells are required for resistance to Mycobacterium tuberculosis infection Proc Natl Acad Sci USA 89 1201312017.

    • Search Google Scholar
    • Export Citation
  • 20. Y. Ozeki 2010 Transient role of CD4+CD25+ regulatory T cells in mycobacterial infection in mice Int Immunol 22 179189.

  • 21. D. Smith 1997 T-cell-independent granuloma formation in response toMycobacteriumavium: role of tumour necrosis factoralpha and interferon-gamma Immunology 92 413421.

    • Search Google Scholar
    • Export Citation
  • 22. P.J. Maglione J. Xu J. Chan 2007 B cells moderate inflammatory progression and enhance bacterial containment upon pulmonary challenge with Mycobacterium tuberculosis J Immunol 178 72227234.

    • Search Google Scholar
    • Export Citation
  • 23. A.M. Cooper 2009 Cell-mediated immune responses in tuberculosis Annu Rev Immunol 27 393422.

  • 24. C.A. Scanga 2000 Depletion of CD4(+) T cells causes reactivation of murine persistent tuberculosis despite continued expression of interferon gamma and nitric oxide synthase 2 J Exp Med 192 347358.

    • Search Google Scholar
    • Export Citation
  • 25. C. Aagaard 2009 Protection and polyfunctional T cells induced by Ag85B-TB10.4/IC31 against Mycobacterium tuberculosis is highly dependent on the antigen dose PLoS One 4 e5930.

    • Search Google Scholar
    • Export Citation

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Editor(s)-in-Chief: Dunay, Ildiko Rita

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Chair of the Editorial Board:
Jeffrey S. Buguliskis (Thomas Jefferson University, USA)

  • Jörn Albring (University of Münster, Germany)
  • Stefan Bereswill (Charité - University Medicine Berlin, Germany)
  • Dunja Bruder (University of Megdeburg, Germany)
  • Jan Buer (University of Duisburg, Germany)
  • Jeff Buguliskis (Thomas Jefferson University, USA)
  • Edit Buzas (Semmelweis University, Hungary)
  • Charles Collyer (University of Sydney, Australia)
  • Renato Damatta (UENF, Brazil)
  • Ivelina Damjanova (Semmelweis University, Hungary)
  • Maria Deli (Biological Research Center, HAS, Hungary)
  • Olgica Djurković-Djaković (University of Belgrade, Serbia)
  • Jean-Dennis Docquier (University of Siena, Italy)
  • Anna Erdei (Eötvös Loránd University, Hungary)
  • Zsuzsanna Fabry (University of Washington, USA)
  • Beniam Ghebremedhin (Witten/Herdecke University, Germany)
  • Nancy Guillen (Institute Pasteur, France)
  • Georgina L. Hold (University of Aberdeen, United Kingdom)
  • Ralf Ignatius (Charité - University Medicine Berlin, Germany)
  • Zsuzsanna Izsvak (MDC-Berlin, Germany)
  • Achim Kaasch (University of Cologne, Germany)
  • Tamás Laskay (University of Lübeck, Germany)
  • Oliver Liesenfeld (Roche, USA)
  • Shreemanta Parida (Vaccine Grand Challenge Program, India)
  • Matyas Sandor (University of Wisconsin, USA)
  • Ulrich Steinhoff (University of Marburg, Germany)
  • Michal Toborek (University of Miami, USA)
  • Mary Jo Wick (University of Gothenburg, Sweden)
  • Susanne A. Wolf (MDC-Berlin, Germany)


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