title: Mice from a genetically resistant background lacking the interferon gamma receptor are susceptible to infection with Leishmania major but mount a polarized T helper cell 1-type CD4+ T cell response.
abstract: Mice with homologous disruption of the gene coding for the ligand-binding chain of the interferon (IFN) gamma receptor and derived from a strain genetically resistant to infection with Leishmania major have been used to study further the role of this cytokine in the differentiation of functional CD4+ T cell subsets in vivo and resistance to infection. Wild-type 129/Sv/Ev mice are resistant to infection with this parasite, developing only small lesions, which resolve spontaneously within 6 wk. In contrast, mice lacking the IFN-gamma receptor develop large, progressing lesions. After infection, lymph nodes (LN) and spleens from both wild-type and knockout mice showed an expansion of CD4+ cells producing IFN-gamma as revealed by measuring IFN-gamma in supernatants of specifically stimulated CD4+ T cells, by enumerating IFN-gamma-producing T cells, and by Northern blot analysis of IFN-gamma transcripts. No biologically active interleukin (IL) 4 was detected in supernatants of in vitro-stimulated LN or spleen cells from infected wild-type or deficient mice. Reverse transcription polymerase chain reaction analysis with primers specific for IL-4 showed similar IL-4 message levels in LN from both types of mice. The IL-4 message levels observed were comparable to those found in similarly infected C57BL/6 mice and significantly lower than the levels found in BALB/c mice. Anti-IFN-gamma treatment of both types of mice failed to alter the pattern of cytokines produced after infection. These data show that even in the absence of IFN-gamma receptors, T helper cell (Th) 1-type responses still develop in genetically resistant mice with no evidence for the expansion of Th2 cells.
authors.affiliation: World Health Organization Immunology Research and Training Center, University of Lausanne, Epalinges, Switzerland.
authors.forename: K
authors.initials: K
authors.lastname: Swihart
authors.forename: U
authors.initials: U
authors.lastname: Fruth
authors.forename: N
authors.initials: N
authors.lastname: Messmer
authors.forename: K
authors.initials: K
authors.lastname: Hug
authors.forename: R
authors.initials: R
authors.lastname: Behin
authors.forename: S
authors.initials: S
authors.lastname: Huang
authors.forename: G
authors.initials: G
authors.lastname: Del Giudice
authors.forename: M
authors.initials: M
authors.lastname: Aguet
authors.forename: J A
authors.initials: JA
authors.lastname: Louis
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000502:physiology*; D018664:Interleukin-12 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D018320:Leishmania major; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017471:Receptors, Interferon / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D017471:Receptors, Interferon; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma