title: TNF receptor p55 is required for elimination of inflammatory cells following control of intracellular pathogens.
abstract: The elimination of lymphocytes within inflammatory lesions is a critical component in the resolution of disease once pathogens have been cleared. We report here that signaling through the TNF receptor p55 (TNFRp55) is required to eliminate lymphocytes from lesions associated with intracellular pathogens. Thus, TNFRp55-/- mice, but not Fas-deficient mice, maintained inflammatory lesions associated with either Leishmania major or Rhodococcus equi infection, although they developed a Th1 response and controlled the pathogens. Inflammatory cells from either L. major- or R. equi-infected C57BL/6 mice were sensitive to TNF-induced apoptosis, and conversely the number of apoptotic cells in the lesions from TNFRp55-/- mice was dramatically reduced compared with wild-type mice. Furthermore, in vivo depletion of TNF in wild-type mice blocked lesion regression following R. equi infection. Taken together, our results suggest that signaling through the TNFRp55, but not Fas, is required to induce apoptosis of T cells within inflammatory lesions once pathogens are eliminated, and that in its absence lesions fail to regress.
authors.affiliation: Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia 19104, USA.
authors.forename: S T
authors.initials: ST
authors.lastname: Kanaly
authors.forename: M
authors.initials: M
authors.lastname: Nashleanas
authors.forename: B
authors.initials: B
authors.lastname: Hondowicz
authors.forename: P
authors.initials: P
authors.lastname: Scott
mesh_terms: D000193:Actinomycetales Infections / Q000209:etiology / Q000276:immunology / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000382:microbiology / Q000469:parasitology; D007424:Intracellular Fluid / Q000382:microbiology / Q000469:parasitology; D018320:Leishmania major / Q000276:immunology / Q000472:pathogenicity*; D016773:Leishmaniasis, Cutaneous / Q000209:etiology / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D016929:Rhodococcus equi / Q000276:immunology / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology; D019014:fas Receptor / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor