TY - JOUR A1 - Bogdan, Christian A1 - Moll, Heidrun A1 - Solbach, Werner A1 - Röllinghoff, Martin T1 - Tumor necrosis factor-\(\alpha\) in combination with interferon-\(\gamma\), but not with interleukin 4 activates murine macrophages for elimination of Leishmania major amastigotes N2 - We have previously shown that during an infection with Leishmania major, susceptible BALB/c mice, as opposed to mice of a resistant strain (C57BLl6), are primed by lipopolysaccharide for the production of high levels of tumor necrosis factor-\(\alpha\) (TNF-\(\alpha\)) which is known to be a potent maerophage M\(\Phi\) stimulator in other parasitic diseases. In the present study we investigated whether TNF-\(\alpha\) activates M\(\Phi\) for killing of L. major parasites. In the absence of interferon-y (IFN-\(\gamma\)) or lipopolysaccharide, TNF-\(\alpha\) (0.025-25000 U/ml) failed to activate peritoneal exudate M\(\Phi\) from BALB/c mice for killling of L. major amastigotes. In the presence of suboptimal doses of IFN-\(\gamma\) (5 or 10 Vlml), however, TNF-\(\alpha\) mediated a rapid elimination of intracellular parasites, which was highly significant compared to IFN-\(\gamma\) alone. Tbe combination of TNF with interleukin 4, in contrast, was inactive in this respect and allowed survival of intracellular parasites. From these data we conelude that the presence of IFN-\(\gamma\) is crucial for TNF-\(\alpha\)-mediated killing of L. major parasites by M\(\Phi\). Disease progression in susceptible mice therefore seems to be a consequence of a deficiency of IFN-\(\gamma\) and a predominance of interleukin 4 rather than the result of an excess amount of TNF-\(\alpha\). KW - Infektionsbiologie Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-31614 VL - 20 SP - 1131 EP - 1135 ER - TY - JOUR A1 - Moll, Heidrun A1 - Fuchs, Harald A1 - Blank, Christine A1 - Röllinghoff, Martin T1 - Langerhans cells transport Leishmania major from the infected skin to the draining lymph node for presentation to antigen-specific T cells N2 - No abstract available KW - Immunologie KW - Langerhans cell KW - Leishmania major KW - T-cell Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-46023 ER - TY - JOUR A1 - Solbach, Werner A1 - Moll, Heidrun A1 - Röllinghoff, Martin T1 - Lymphocytes play the music but the macrophage calls the tune N2 - No abstract available KW - Immunologie Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-45889 ER - TY - JOUR A1 - Blank, Christine A1 - Fuchs, Harald A1 - Rappersberger, Klemens A1 - Röllinghoff, Martin A1 - Moll, Heidrun T1 - Parasitism of epidermal Langerhans cells in experimental cutaneous leishmaniasis with Leishmania major N2 - Murine epidermal Langerhans cells (LC) have been demonstrated to stimulate a vigorous T cell response to Leishmania major, a cause of human cutaneous leishmaniasis. It was therefore of interest to analyze whether LC can take up viable parasites. Epidermal cells were obtained from mouse ear skin for incubation with L. major and subsequent detection of intracellular parasites by cytochemistry. Freshly isolated LC, but not cultured LC, phagocytosed L. major and the uptake was inhibited by antibodies to the complement receptor type 3. Electron microscopic studies revealed the presence of viable amastigotes within Le. Moreover, with double-Iabeling techniques, L. major-containing LC could also be detected in infected skin. The results demonstrate that LC can internalize L. major. Since the number of organisms per infected LC remained consistently low, the prime task of LC may not be the promotion of parasite spreading but the presentation of L. major antigen to T cells and, thus, the regulation of the cellular immunity during cutaneous leishmaniasis. Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-45850 ER - TY - JOUR A1 - Moll, Heidrun A1 - Binöder, Kerstin A1 - Bogdan, Christian A1 - Solbach, Werner A1 - Röllinghoff, Martin T1 - Production of tumour necrosis factor during murine cutaneous leishmaniasis N2 - We have assessed the role of tumour necrosis factor-a (TNF) during cutaneous leishmaniasis and demonstrated that significant levels of TNF were released by spleen cells from infected mice after in cirro restimulation with Leishmania major promastigotes. Spleen cells from both genetically resistant and genetically susceptible mice were equally capable of producing TNF. After challenge with bacterial endotoxin, TNF activity could also be demonstrated in the serum of L. mujor-infected mice and the titres correlated with the course of cutaneous disease in susceptible and resistant mice. TNF did not exert a direct leishmanicidal effect in uitro. Furthermore, our study indicated that macrophages are the source of L. major-induced TNF activity and that its elicitation is dependent on the presence of T cells. These findings suggest that TNF acts in concert with other cytokines produced during L. major infection and that its role depends on the composition of T cell subsets and cytokines present. KW - Immunologie Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61291 ER - TY - JOUR A1 - Moll, Heidrun A1 - Röllinghoff, Martin T1 - Resistance to murine cutaneous leishmaniasis is mediated by T\(_H\)1 cells, but disease-promoting CD4\(^+\) cells are different from T\(_H\)2 cells N2 - No abstract available KW - Biologie KW - Immunologie Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61305 ER - TY - JOUR A1 - Moll, Heidrun A1 - Müller, Christoph A1 - Gillitzer, Reinhard A1 - Fuchs, Harald A1 - Röllinghoff, Martin A1 - Simon, Markus M. A1 - Kramer, Michael D. T1 - Expression of T-cell-associated serine proteinase-1 during murine Leishmania major infection correlates with susceptibility to disease N2 - The expression of T-cell-associated serine proteinase 1 (MTSP-1) in vivo during Leishmania major infection was analyzed in genetically resistant C57BL/6 mice and in genetically susceptible BALB/c mice. Using a monoclonal antibody as well as an RNA probe specific for MTSP-1 to stain tissue sections, we found T cells expressing MTSP-1 in skin lesions and spleens of mice of both strains. In skin lesions, MTSP-1-positive T cells could be detected as early as 3 days after infection. Most importantly, the frequency of T cells expressing MTSP-1 was significantly higher in susceptible BALB/c mice than in resistant C57BL/6 mice. These findings suggest that MTSP-1 is associated with disease-promoting T cells and that it may be an effector molecule involved in the pathogenesis of cutaneous leishmaniasis. KW - Biologie KW - Immunologie Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61311 ER - TY - JOUR A1 - Moll, Heidrun A1 - Röllinghoff, Martin T1 - T-cell reactivity to purified lipophosphoglycan from Leishmania major: A model for analysis of the cellular immune response to microbial carbohydrates. N2 - The major macromolecule on the surface o/Leishmania majorpromastigotes is a lipophosphoglycan (LPG). This glycoconjugate plays a key role in determining infectivity and survival of para-sites in the mammalian host cell. In addition, L. major LPG is able to induce a host-protective immune response. In this article, we summarise the evidence for recognition of highly purified LPG by T cells and we discuss the potential mechanisms of T-cell Stimulation by this non-protein antigen. KW - Leishmania KW - T lymphocytes KW - glycosyl phosphatidyl-inostitols. Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-33022 ER -