Expansion and function of Foxp3-expressing T regulatory cells during tuberculosis.
Mycobacterium tuberculosis (Mtb) frequently establishes persistent infections that may be facilitated by mechanisms that dampen immunity. T regulatory (T reg) cells, a subset of CD4(+) T cells that are essential for preventing autoimmunity, can also suppress antimicrobial immune responses. We use Foxp3-GFP mice to track the activity of T reg cells after aerosol infection with Mtb. We report that during tuberculosis, T reg cells proliferate in the pulmonary lymph nodes (pLNs), change their cell surface phenotype, and accumulate in the pLNs and lung at a rate parallel to the accumulation of effector T cells. In the Mtb-infected lung, T reg cells accumulate in high numbers in all sites where CD4(+) T cells are found, including perivascular/peribronchiolar regions and within lymphoid aggregates of granulomas. To determine the role of T reg cells in the immune response to tuberculosis, we generated mixed bone marrow chimeric mice in which all cells capable of expressing Foxp3 expressed Thy1.1. When T reg cells were depleted by administration of anti-Thy1.1 before aerosol infection with Mtb, we observed approximately 1 log less of colony-forming units of Mtb in the lungs. Thus, after aerosol infection, T reg cells proliferate and accumulate at sites of infection, and have the capacity to suppress immune responses that contribute to the control of Mtb.
Scott-Browne
James P
JP
Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.
Shafiani
Shahin
S
Tucker-Heard
Glady's
G
Ishida-Tsubota
Kumiko
K
Fontenot
Jason D
JD
Rudensky
Alexander Y
AY
Bevan
Michael J
MJ
Urdahl
Kevin B
KB
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002465:Cell Movement; D049109:Cell Proliferation; D002678:Chimera; D015169:Colony Count, Microbial; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006099:Granuloma / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000096:biosynthesis; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*; D015854:Up-Regulation / Q000235:genetics
D015415:Biomarkers; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016753:Interleukin-10
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