title: Mycobacterium tuberculosis-specific CD4+, IFNgamma+, and TNFalpha+ multifunctional memory T cells coexpress GM-CSF.
abstract: Multifunctional T cells expressing several cytokines in parallel are thought to play a crucial role in protection against different infections. To characterize T cell cytokine patterns associated with disease and protection in Mycobacterium tuberculosis infection we determined the expression of IFNgamma, IL-2, TNFalpha, and GM-CSF in T cell subpopulations from children with tuberculosis (TB) and healthy latently M. tuberculosis-infected children (LTBI) after short-term in vitro restimulation. We identified CD4(+) effector memory T cells (T(EM)) as the major source of all measured cytokines after antigen-specific restimulation. T(EM) from children with TB expressed higher proportions of IFNgamma, TNFalpha, and IL-2 after Mtb restimulation while no differences were detected for GM-CSF between both study groups. GM-CSF secretion strongly depended on antigen-specific stimulation. Analyses of multiple cytokine patterns revealed that the majority of GM-CSF-positive M. tuberculosis-specific memory T cells coexpressed IFNgamma and TNFalpha therefore showing a characteristic feature of multifunctional T cells. We conclude that children with active TB possess higher proportions of IFNgamma-, TNFalpha-, and/or IL-2-positive T(EM) than children with LTBI while GM-CSF coexpression reveals a novel subpopulation within CD4(+) memory T cells not increased in children with active TB.
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Mueller
authors.forename: Anne K
authors.initials: AK
authors.lastname: Detjen
authors.forename: Sebastian D
authors.initials: SD
authors.lastname: Schuck
authors.forename: Andrea
authors.initials: A
authors.lastname: Gutschmidt
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wahn
authors.forename: Klaus
authors.initials: K
authors.lastname: Magdorf
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
authors.forename: Marc
authors.initials: M
authors.lastname: Jacobsen
mesh_terms: D000293:Adolescent; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007223:Infant; D007371:Interferon-gamma / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000276:immunology; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017493:Leukocyte Common Antigens