Activated T cells induce macrophages to produce NO and control Leishmania major in the absence of tumor necrosis factor receptor p55.
The ability to activate macrophages in vitro for nitric oxide production and killing of Leishmania major parasites is dependent on tumor necrosis factor, although L. major-infected mice lacking the TNF receptor p55 (TNFRp55(-/-) mice) or both the TNFRp55 and TNFRp75 (TNFRp55p75(-/-) mice) are able to produce NO in vivo and eliminate the parasites. Here we report that activated T cells cocultured with macrophages results in TNFR-independent activation sufficient to control parasites and that both CD40/CD40L and LFA-1 contribute to T-cell-mediated macrophage activation. Thus, anti-CD3-stimulated T cells activated TNFR-deficient macrophages, while T cells from CD40L(-/-) mice were partially defective in triggering NO production by TNFRp55p75(-/-) macrophages. Moreover, in the presence of gamma interferon, anti-CD40 monoclonal antibody (MAb) activated TNFR-deficient macrophages. Finally, MAb blockade of LFA-1 completely inhibited macrophage NO production. Our data indicate that T cells can activate macrophages in the absence of TNF, thus providing a mechanism for how TNFR-deficient mice can control intracellular pathogens.
Nashleanas
M
M
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Scott
P
P
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D019013:CD40 Antigens / Q000502:physiology; D023201:CD40 Ligand; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D018320:Leishmania major / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D008264:Macrophages / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis*; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D013601:T-Lymphocytes / Q000502:physiology*
D015703:Antigens, CD; D019013:CD40 Antigens; D008070:Lipopolysaccharides; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D018799:Intercellular Adhesion Molecule-1; D023201:CD40 Ligand; D009569:Nitric Oxide; D007371:Interferon-gamma