Activated T cells induce macrophages to produce NO and control Leishmania major in the absence of tumor necrosis factor receptor p55.
Publication/Presentation Date
3-1-2000
Abstract
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.
Volume
68
Issue
3
First Page
1428
Last Page
1434
ISSN
0019-9567
Published In/Presented At
Nashleanas, M., & Scott, P. (2000). Activated T cells induce macrophages to produce NO and control Leishmania major in the absence of tumor necrosis factor receptor p55. Infection and immunity, 68(3), 1428–1434. https://doi.org/10.1128/IAI.68.3.1428-1434.2000
Disciplines
Medicine and Health Sciences
PubMedID
10678956
Department(s)
Department of Medicine
Document Type
Article