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Original Article |
T Cells Cytotoxic for Activated Macrophages
Correspondence to: Simon R. Carding, The University of Leeds, School of Biochemistry and Molecular Biology, Leeds LS2 9JT, W. Yorkshire, England, UK. Tel:44-0113-233-1404 Fax:44-0113-233-1421 E-mail:S.R.Carding{at}bmb.leeds.ac.uk.
Although T cells are involved in the regulation of inflammation after infection, their precise function is not known. Intraperitoneal infection of T cell receptor (TCR)--/- mice with the intracellular bacterium Listeria monocytogenes resulted in the development of necrotic foci in the livers. In contrast, the peritoneal cavities of infected TCR--/- mice contained an accumulation of low density activated macrophages and a reduced percentage of macrophages undergoing apoptosis. T cell hybridomas derived from mice infected with Listeria were preferentially stimulated by low density macrophages from peritoneal exudates of infected mice. Furthermore, primary splenic T cells isolated from Listeria-infected mice were cytotoxic for low density macrophages in vitro, and cytotoxicity was inhibited in the presence of antibodies to the TCR. These results demonstrate a novel interaction between T cells and activated macrophages in which T cells are stimulated by terminally differentiated macrophages to acquire cytotoxic activity and which, in turn, induce macrophage cell death. This interaction suggests that T cells regulate the inflammatory response to infection with intracellular pathogens by eliminating activated macrophages at the termination of the response.
Key Words: T lymphocyte, macrophages, apoptosis, inflammation, cell-mediated immunity
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