title: Cutting Edge: Regulatory T cells prevent efficient clearance of Mycobacterium tuberculosis.
abstract: Mycobacterium tuberculosis remains one of the top microbial killers of humans causing approximately 2 million deaths annually. More than 90% of the 2 billion individuals infected never develop active disease, indicating that the immune system is able to generate mechanisms that control infection. However, the immune response generally fails to achieve sterile clearance of bacilli. Using adoptive cell transfer into C57BL/6J-Rag1(tm1Mom) mice (Rag1(-/-)), we show that regulatory T cells prevent eradication of tubercle bacilli by suppressing an otherwise efficient CD4+ T cell response. This protective CD4+ T cell response was not correlated with increased numbers of IFN-gamma- or TNF-alpha-expressing cells or general expression levels of IFN-gamma or inducible NO synthase in infected organs compared with wild-type C57BL/6 animals. Furthermore, suppression of protection by cotransferred regulatory T cells was neither accompanied by a general increase of IL-10 expression nor by higher numbers of IL-10-producing CD4+ T cells.
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany. kursar@mpiib-berlin.mpg.de
authors.forename: Mischo
authors.initials: M
authors.lastname: Kursar
authors.forename: Markus
authors.initials: M
authors.lastname: Koch
authors.forename: Hans-Willi
authors.initials: HW
authors.lastname: Mittrücker
authors.forename: Geraldine
authors.initials: G
authors.lastname: Nouailles
authors.forename: Kerstin
authors.initials: K
authors.lastname: Bonhagen
authors.forename: Thomas
authors.initials: T
authors.lastname: Kamradt
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D019001:Nitric Oxide Synthase / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D018398:Homeodomain Proteins; D014409:Tumor Necrosis Factor-alpha; C064658:RAG-1 protein; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase