IL‐12 eliminates the Th‐2 dependent protective immune response of mice to larval Strongyloides stercoralis

The goal of the present study was to determine if immune‐mediated killing of S. stercoralis L3 in mice could be modulated by shifting from a Th‐2 to a Th‐1 type immune response. L3 killing in immunized mice was ablated in CD4+ T cell‐depleted animals, but not in CD8+ T cell‐depleted or β2‐microglobu...

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Bibliographic Details
Published in:Parasite immunology 1997-01, Vol.19 (1), p.29-39
Main Authors: ROTMAN, H.L., SCHNYDER‐CANDRIAN, S., SCOTT, P., NOLAN, T.J., SCHAD, G.A., ABRAHAM, D.
Format: Article
Language:English
Subjects:
AIDS/HIV
Animals
CD8-Positive T-Lymphocytes - immunology
Dogs
Enzyme-Linked Immunosorbent Assay
Eosinophil Peroxidase
IL‐12
Immunity - drug effects
Immunization
Interleukin-12 - pharmacology
Interleukin-4 - pharmacology
Interleukin-5 - pharmacology
Larva - immunology
Lymphocyte Depletion
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
nematode
Peroxidases - analysis
Strongyloides stercoralis
Strongyloides stercoralis - immunology
Strongyloidiasis - immunology
Strongyloidiasis - prevention & control
T-Lymphocytes, Helper-Inducer
Th2 Cells - immunology
Th‐2 immunity
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Summary:The goal of the present study was to determine if immune‐mediated killing of S. stercoralis L3 in mice could be modulated by shifting from a Th‐2 to a Th‐1 type immune response. L3 killing in immunized mice was ablated in CD4+ T cell‐depleted animals, but not in CD8+ T cell‐depleted or β2‐microglobulin‐deficient mice. Treatment of immunized mice with IL‐4 or IL‐5 neutralizing MoAb significantly reduced the protective effects of vaccination against S. stercoralis, while protective immunity was unimpaired in IFN‐γ knockout mice. Recombinant IL‐12 was administered to infected mice to switch the immune response from a Th‐2 to a Th‐1 type response. Protective immunity was ablated in immunized mice that received IL‐12 therapy. Eosinophil numbers, eosinophil peroxidase levels, and parasite‐specific IgG1 levels were lowered in IL‐12 treated immunized animals, and parasite‐specific IgG2a levels were increased in these animals. The data indicate that eosinophils are important as mediators of larval killing, and that the establishment of Th‐2 type immunity results in killing of infective S. stercoralis L3, while a shift to Th‐1 type immunity abrogates protective responses.
ISSN:0141-9838
1365-3024
DOI:10.1046/j.1365-3024.1997.d01-142.x