ABSTRACT
GITR (glucocorticoid-induced TNF receptor) is a recently identified member of the TNF receptor superfamily. The receptor is preferentially expressed on CD4+CD25+ regulatory T cells and GITR signals break the suppressive activity of the subset. In this study, we wanted to reveal the in vivo function of GITR in herpes simplex virus type 1 (HSV-1) infection. A single injection of anti-GITR mAb (DTA-1) immediately after viral infection significantly increased the number of CD4+ and CD8+ T cells expressing CD25, an activation surface marker, and secreting IFN-gamma. We confirmed these in vivo observations by showing ex vivo that re-stimulation of CD4+ or CD8+ T cells with a CD4+ or CD8+ T-cell-specific HSV-1 peptide, respectively, induced a significant elevation in cell proliferation and in IFN-gamma secretion. Our results indicate that GITR signals play a critical role in the T-cell immunity to HSV-1.
Subject(s)
Animals , Female , Mice , Antibodies, Monoclonal/pharmacology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cell Proliferation , Glucocorticoids/pharmacology , Herpes Simplex/immunology , Herpesvirus 1, Human/pathogenicity , Immunity, Cellular , Interferon-gamma/metabolism , Lymphocyte Activation , Mice, Inbred BALB C , Peptide Fragments/metabolism , Receptors, Interleukin-2/metabolism , Receptors, Nerve Growth Factor/genetics , Receptors, Tumor Necrosis Factor/genetics , T-Lymphocytes/immunologyABSTRACT
The evolution of Mycobacterium tuberculosis as an intracellular pathogen has led to a complex relationship between it and its host, the human mononuclear phagocyte. The products of M. tuberculosis-specific T lymphocytes are essential for macrophage activation for intracellular mycobacterial killing. However, dysfunction cell-mediated immune response to infection with M. tuberculosis may contribute to progressive primary infection or reactivation of endogenous foci of mycobacteria. Th1 cells produce IL-2, which is essential for proper cellular immunity. The aim of this study was to identify the variation in IL-2 activity and soluble IL-2 receptor (IL-2 R) in peripheral blood lymphocyte in patients suffering with pulmonary tuberculosis. A significant decrease in IL-2 and IL-2 receptor level was observed in patients with pulmonary tuberculosis when compared to normal controls. Our results suggested that patients with pulmonary tuberculosis had a defect in IL-2 production. Better understanding of these interactions will allow the development of increasingly specific immune-based interventions for prevention and treatment of tuberculosis.
Subject(s)
Adolescent , Adult , Case-Control Studies , Female , Humans , Interleukin-2/biosynthesis , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Receptors, Interleukin-2/metabolism , Tuberculosis, Pulmonary/bloodABSTRACT
This paper reports the overall effects of three lectins, extracted from Canavalia brasiliensis, Dioclea violacea, and D. grandiflora, on BALB/c mice popliteal draining lymph nodes. These lectins have presented high stimulatory capacity on lymph node T cells. Additionally, they were able to induce apoptosis and inflammation (frequently associated with high endothelial venule necrosis). The data presented here suggest that the Diocleinae lectins studied can stimulate in vivo T cell activation and apoptosis, as well as present important side effects
Subject(s)
Animals , Mice , Male , Female , Apoptosis/drug effects , Fabaceae/chemistry , Lectins/pharmacology , Lymph Nodes/drug effects , Lymphocyte Activation/drug effects , Amino Acid Sequence , Cell Count , Endothelium/blood supply , Fabaceae/genetics , Inflammation/chemically induced , Lymph Nodes/pathology , Mice, Inbred BALB C , Necrosis , Receptors, Interleukin-2/metabolism , Venules/pathologyABSTRACT
1. We have shown that nonsteroidal anti-inflammatory drugs are potent inhibitors of neutrophil activation. tenoxican is a new compound of the oxican family which has been shown to be effective for routine clinical use. 2. In the present study we examined the immune pharmacological effects of this compound on lymphocyte function by determining its efffect on the expression of IL-2 receptors, on monocyte function by looking at chemotaxis and IL-1 release and on release and on neutrophil function by evaluating the chemotactic response to a standard stimulus. 3. The data show that Tenoxican inhibits the neutrophil and monocyte functional chemotactic response in vitro, and to some extent in vivo for monocytes, but has no effect onthe expression of IL-2 receptors or IL-1 release. Tenoxicam inhibits the mobilization of neutrophils and monocytes to inflamatory sites, even thought this effect was not clearly demonstrable when cells were tested after oral use