title: Mycobacterial trehalose-containing glycolipid with immunomodulatory activity on human CD4+ and CD8+ T-cells.
abstract: Protection against Mycobacterium tuberculosis is based on cell-mediated immunity, most importantly involving CD4+ and CD8+ T-cell subsets. One of the key features of the tubercle bacillus is its cell envelope, characterized by extremely abundant and specific lipids. The cell-surface glycolipid 2,3-di-O-acyl-trehalose (DAT) has been consistently found in M. tuberculosis strains. In this study, analysis of proliferation, activation markers and cytokine release was performed in human peripheral blood mononuclear cells (PBMC) activated in the presence and absence of DAT. We present evidence that mycobacterial DAT is able to reduce antigen-induced proliferation of human CD4+ and CD8+ T-cell subsets. We show that the effect is associated with a decrease of cells expressing the T-cell surface activation markers CD25 and CD69, and down-modulation of IL-2, IL-12, TNF-alpha and IL-10 cytokines. Data indicating that fine acyl chain structural variations in the trehalose-containing lipid may be involved in the degree of immune modulation are also presented.
authors.affiliation: Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apdo. Postal 70-228, Coyoacán, 04510 D.F. Mexico, Mexico.
authors.forename: Rafael
authors.initials: R
authors.lastname: Saavedra
authors.forename: Erika
authors.initials: E
authors.lastname: Segura
authors.forename: Eda P
authors.initials: EP
authors.lastname: Tenorio
authors.forename: Luz M
authors.initials: LM
authors.lastname: López-Marín
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D006017:Glycolipids / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D037181:Lectins, C-Type; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D019907:Mycobacterium fortuitum / Q000737:chemistry / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000737:chemistry* / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D014199:Trehalose; D000099192:CD69 Antigens
chemical_list: D000942:Antigens, Bacterial; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D006017:Glycolipids; D037181:Lectins, C-Type; D015375:Receptors, Interleukin-2; D014199:Trehalose; D000099192:CD69 Antigens; C082079:glycolipid IV, Mycobacterium tuberculosis