title: Modulation of human T cell cytokines by the Mycobacterium tuberculosis-secreted protein Wag31.
abstract: Mycobacterium tuberculosis secretes a number of proteins into the extracellular milieu during growth. Several of these proteins have been associated with modulation of the host immune response. Antigen 84, or Wag31, is one such protein that is conserved among all mycobacterial species and is recognized by the sera from tuberculosis and leprosy patients. Here, we examined the effect of Wag31 on the ability of activated human T cells to produce cytokines such as IL-10, IL-17 and IFN-γ in response to combined anti-CD3 and anti-CD28 stimulation. Purified recombinant Wag31 inhibited the secretion of IL-10 and IL-17, but not IFN-γ, by human T cells stimulated with plate-bound anti-CD3 and anti-CD28 monoclonal antibodies. Furthermore, the C-terminal domain, but not the N-terminal domain, inhibited the production of IL-10 and IL-17 without a significant effect on the production of IFN-γ. These data suggest that Wag31 may modulate human T cell immune responses during tuberculosis infection through its C-terminal domain.
authors.affiliation: Department of Pulmonary Immunology, The University of Texas Health Science Center, Tyler, TX 75708-3154, USA. Electronic address: buka.samten@uthct.edu.
authors.forename: Buka
authors.initials: B
authors.lastname: Samten
authors.affiliation: Department of Molecular and Cellular Biochemistry, The University of Texas Health Science Center, Tyler, TX 75708-3154, USA.
authors.forename: Stewart
authors.initials: S
authors.lastname: Fannin
authors.affiliation: Department of Molecular and Cellular Biochemistry, The University of Texas Health Science Center, Tyler, TX 75708-3154, USA.
authors.forename: Krishna
authors.initials: K
authors.lastname: Sarva
authors.affiliation: Department of Pulmonary Immunology, The University of Texas Health Science Center, Tyler, TX 75708-3154, USA.
authors.forename: Na
authors.initials: N
authors.lastname: Yi
authors.affiliation: Department of Molecular and Cellular Biochemistry, The University of Texas Health Science Center, Tyler, TX 75708-3154, USA.
authors.forename: Murty
authors.initials: M
authors.lastname: Madiraju
authors.affiliation: Department of Molecular and Cellular Biochemistry, The University of Texas Health Science Center, Tyler, TX 75708-3154, USA. Electronic address: malinir1@gmail.com.
authors.forename: Malini
authors.initials: M
authors.lastname: Rajagopalan
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D000072417:Protein Domains; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; C573415:IFNG protein, human; C508609:IL10 protein, human; D020381:Interleukin-17; C000591547:Wag31 protein, Mycobacterium tuberculosis; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: Antigen 84; Cytokines; T cells; Tuberculosis; Wag31