PMID: 2104918Jan 1, 1990Paper

Cure of murine leishmaniasis with anti-interleukin 4 monoclonal antibody. Evidence for a T cell-dependent, interferon gamma-independent mechanism

The Journal of Experimental Medicine
M D SadickR M Locksley

Abstract

BALB/c mice infected with Leishmania major develop fatal, progressive disease, despite an immune response characterized by expansion of CD4+ T cells in the draining lymph nodes. The immune response has been further characterized by a lack of IFN-gamma mRNA, but increased IL-4 mRNA in lymphoid tissues, and striking elevation of serum IgE. Treatment of infected BALB/c mice with rIFN-gamma at doses shown to be beneficial in other protozoan infections was insufficient to ameliorate L. major infection. In contrast, neutralization of IL-4 by six weekly injections of mAb 11B11 led to attenuation of disease in 100% of animals, and complete cure in 85%. Resolution of disease required the presence of T cells, and recovered mice remained resistant to reinfection at 12 wk. This immunity was adoptively transferable and was dependent on both CD4+ and CD8+ cells. Although administration of anti-IL-4 was associated with fourfold increase in IFN-gamma mRNA in lymph node cells draining the lesion, the coadministration of neutralizing R4 6A2 anti-IFN-gamma mAb had no effect on resistance to disease. This was in marked contrast to resolution of disease in both resistant C57BL/6- and GK1.5-pretreated BALB/c mice that was abrogated by in vivo treatm...Continue Reading

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Citations

Jul 14, 1999·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·D J Fowell, R M Locksley
Dec 1, 1993·Journal of Cellular Biochemistry·S L Reiner, R M Locksley
Feb 10, 2000·Springer Seminars in Immunopathology·C Infante-Duarte, T Kamradt
Nov 1, 1996·Transgenic Research·N Noben-TrauthB Ledermann
Jan 1, 1996·International Journal of Clinical & Laboratory Research·S Romagnani
Jan 1, 1997·Biotherapy·P H van der Meide, H Schellekens
May 1, 1993·Trends in Pharmacological Sciences·F Powrie, R L Coffman
Nov 1, 1990·Journal of Virological Methods·M P Langford, R Kaiwar
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Jul 1, 1995·Parasitology Today·G MilonJ A Louis
Sep 1, 1996·Clinics in Dermatology·S McSorleyF Y Liew
Jan 1, 1991·Research in Immunology·R M LocksleyM D Sadick
Sep 1, 1995·Research in Immunology·D J FowellR M Locksley
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