title: Leptin deficiency in vivo enhances the ability of splenic dendritic cells to activate T cells.
abstract: Leptin is a pleiotropic adipokine that is critical for regulating food intake and energy expenditure and also participates in functions of the immune system, including those of antigen-presenting cells. Here, we assess the effect of leptin deficiency on the function splenic dendritic cells (sDC). sDC from leptin-deficient mice (Lep(ob)) were evaluated ex vivo for phenotype, ability to respond to inflammatory stimuli, to acquire and process antigens and to activate T cells. The data show that Lep(ob) sDC express activation markers similar to controls and respond similarly to LPS activation or anti-CD40 cross-linking. In addition, antigen acquisition and processing by Lep(ob) sDC was similar to controls. However, Lep(ob) sDC elicited higher production of IFN-γ in mixed lymphocyte reactions and increased production of IL-2 by antigen-specific T-cell hybridoma relative to controls. To assess Lep(ob) sDC activation of T cells in vivo, Lep(ob) and control mice were infected systemically with Mycobacterium avium. Lep(ob) mice were significantly better at neutralizing the infection as measured by splenic bacterial load over time. This was mirrored with an increased percentage of activated T cells in M. avium-infected Lep(ob) mice. Thus, although no changes were detected in sDC phenotype, activation, antigen processing or presentation, these DC surprisingly presented an enhanced ability to activate T cells ex vivo and in vivo. These data demonstrate that leptin can modulate DC function and suggest that leptin may dampen T-cell responsiveness in the physiological setting.
authors: Department of Biological Sciences and Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX 79968-0519, USA.
authors: Oscar
authors: O
authors: Ramirez
authors: Department of Biological Sciences and Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX 79968-0519, USA kgarza@utep.edu.
authors: Kristine M
authors: KM
authors: Garza
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D002452:Cell Count; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D020738:Leptin / Q000172:deficiency* / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009162:Mycobacterium avium / Q000276:immunology; D010641:Phenotype; D054411:Receptors, Leptin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
chemical_list: D020738:Leptin; D054411:Receptors, Leptin
keywords: CD4+ T cells; T-cell activation; cytokines; helper T cells