title: In BALB/c mice, IL-4 production during the initial phase of infection with Leishmania major is necessary and sufficient to instruct Th2 cell development resulting in progressive disease.
abstract: In contrast to intact BALB/c mice, BALB/c mice rendered deficient in Vbeta4+ CD4+ T cells develop a Th1 response to infection with Leishmania major and are resistant. Vbeta4-deficient BALB/c mice are unable to generate the early IL-4 transcription occurring in Vbeta4 Valpha8 CD4+ T cells of BALB/c mice within 1 day of infection. Here we demonstrate that treatment of Vbeta4-deficient BALB/c mice with IL-4 during the first 64 h after infection instructs Th2 cell development and susceptibility to infection. The demonstrated inability of IL-4 to reverse the resistant phenotype of BALB/c mice treated with anti-CD4 mAb the day before infection suggest that these effects of IL-4 require its interaction with CD4+ T cells. In contrast to draining lymph node cells from BALB/c mice, cells from Vbeta4-deficient BALB/c mice remain responsive to IL-12 following infection. Strikingly, administration of IL-4 to Vbeta4-deficient BALB/c mice renders their lymph node cells unresponsive to IL-12 by down-regulating IL-12R beta2-chain expression. This study directly demonstrates that in BALB/c mice IL-4 is necessary and sufficient to initiate the molecular events steering Th2 cell maturation and susceptibility to L. major.
authors.affiliation: World Health Organization Immunology Research and Training Center, Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Himmelrich
authors.forename: P
authors.initials: P
authors.lastname: Launois
authors.forename: I
authors.initials: I
authors.lastname: Maillard
authors.forename: T
authors.initials: T
authors.lastname: Biedermann
authors.forename: F
authors.initials: F
authors.lastname: Tacchini-Cottier
authors.forename: R M
authors.initials: RM
authors.lastname: Locksley
authors.forename: M
authors.initials: M
authors.lastname: Röcken
authors.forename: J A
authors.initials: JA
authors.lastname: Louis
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D018450:Disease Progression; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D007108:Immune Tolerance / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D007274:Injections, Intraperitoneal; D018664:Interleukin-12 / Q000378:metabolism / Q000494:pharmacology; D015847:Interleukin-4 / Q000008:administration & dosage / Q000096:biosynthesis*; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D053707:Receptors, Interleukin-12; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*
chemical_list: C508443:Il12rb2 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12; D015847:Interleukin-4