title: The protective Th1 response in mice is induced in the T-cell zone only three weeks after infection with Leishmania major and not during early T-cell activation.
abstract: The protozoan parasite Leishmania spp. causes clinical pictures ranging in severity from spontaneously healing skin ulcers to systemic disease. The immune response associated with healing involves the differentiation of IFNγ-producing Th1 cells, whereas the non-healing phenotype is associated with IL4-producing Th2 cells. The widespread assumption has been that the T-cell differentiation that leads to a healing or non-healing phenotype is established at the time of T-cell activation early after infection. By selectively analyzing the expression of cytokine genes in the T-cell zones of lymph nodes of resistant (Th1) C57BL/6 mice and susceptible (Th2) BALB/c mice during an infection with Leishmania major in vivo, we show that the early T-cell response does not differ between C57BL/6 mice and BALB/c mice. Instead, Th1/Th2 polarization appears suddenly 3 weeks after infection. At the same time point, the number of parasites increases in lymph nodes of both mouse strains, but about 100-fold more in susceptible BALB/c mice. We conclude that the protective Th1 response in C57BL/6 mice is facilitated by the capacity of their innate effector cells to keep parasite numbers at low levels.
authors.affiliation: Center for Structural and Cell Biology in Medicine, Institute of Anatomy, University of Lübeck, Lübeck, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Barthelmann
authors.forename: Julia
authors.initials: J
authors.lastname: Nietsch
authors.forename: Maike
authors.initials: M
authors.lastname: Blessenohl
authors.forename: Tamas
authors.initials: T
authors.lastname: Laskay
authors.forename: Ger
authors.initials: G
authors.lastname: van Zandbergen
authors.forename: Jürgen
authors.initials: J
authors.lastname: Westermann
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kalies
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D061346:Laser Capture Microdissection; D018320:Leishmania major / Q000276:immunology* / Q000302:isolation & purification; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology / Q000503:physiopathology*; D008198:Lymph Nodes / Q000276:immunology / Q000469:parasitology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012867:Skin / Q000276:immunology / Q000469:parasitology; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D013997:Time Factors
chemical_list: D016207:Cytokines