CD95 is required for the early control of parasite burden in the liver of Leishmania donovani-infected mice


Alexander, CE; Kaye, PM; Engwerda, CR; (2001) CD95 is required for the early control of parasite burden in the liver of Leishmania donovani-infected mice. European journal of immunology, 31 (4). pp. 1199-210. ISSN 0014-2980

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Abstract

In this study we show an increased incidence of T cell apoptosis in the liver and spleen of mice infected with Leishmania donovani. T cells from L. donovani-infected mice were found to be increasingly susceptible to CD95-mediated apoptosis in vitro, compared to controls. To test if suboptimal T cell function resulting from CD95-mediated apoptosis contributes to sustained parasite burden in L. donovani parasitized mice, B6.gld mice (lacking functional CD95 ligand) were infected with L. donovani. Surprisingly, at four different time points no difference in levels of T cell apoptosis in the spleen and liver was found between these mice and controls following intravenous delivery of L. donovani amastigotes, indicating that the CD95 / CD95L interaction is not essential for T cell apoptosis in the L. donovani-infected liver and spleen. However, B6.gld mice were increasingly susceptible to L. donovani infection, associated with less efficient granuloma formation in the liver and uncontrolled parasite growth in the spleen. Late in infection (day 56 post-infection), B6.gld mice had higher numbers of IFN-gamma-producing CD4(+) T cells in the liver and spleen, indicating a role for CD95 signaling in the homeostasis of this subset of cytokine-producing T cells in L. donovani-parasitized mice. Adoptive transfer of CD4(+) and CD8(+) T cells into recombinase activating gene 1 knockout (RAG-1(- / -)) recipients, revealed that CD95L expressed on CD4(+) T cells contributes to early control of L. donovani infection in the liver via mechanisms that are independent of granuloma formation and induction of apoptosis. These results indicate important roles for CD95 and CD95L that are unrelated to regulation of apoptosis in the early control of L. donovani infection.

Item Type: Article
Keywords: Animal, Antigens, CD95/genetics/*immunology, Apoptosis, CD4-Positive T-Lymphocytes/immunology/metabolism/transplantation, Cells, Cultured, Flow Cytometry, Gene Deletion, Genes, RAG-1/genetics, Genetic Predisposition to Disease, Granuloma/immunology/parasitology, In Situ Nick-End Labeling, Interferon Type II/immunology/metabolism, Leishmania donovani/*growth & development/physiology, Leishmaniasis, Visceral/*immunology/parasitology, Liver/immunology/parasitology/pathology, Membrane Glycoproteins/deficiency/genetics/metabolism, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Spleen/immunology, Support, Non-U.S. Gov't, Animal, Antigens, CD95, genetics, immunology, Apoptosis, CD4-Positive T-Lymphocytes, immunology, metabolism, transplantation, Cells, Cultured, Flow Cytometry, Gene Deletion, Genes, RAG-1, genetics, Genetic Predisposition to Disease, Granuloma, immunology, parasitology, In Situ Nick-End Labeling, Interferon Type II, immunology, metabolism, Leishmania donovani, growth & development, physiology, Leishmaniasis, Visceral, immunology, parasitology, Liver, immunology, parasitology, pathology, Membrane Glycoproteins, deficiency, genetics, metabolism, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Spleen, immunology, Support, Non-U.S. Gov't
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Leishmaniasis Group
PubMed ID: 11298345
Web of Science ID: 168090100025
URI: http://researchonline.lshtm.ac.uk/id/eprint/16444

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