Hypereosinophilic syndrome induced by neonatal immunization against MHC class II alloantigen: critical role of IL-4.
A significant proportion of patients with the hypereosinophilic syndrome suffer from oligoclonal expansion of type 2 helper T lymphocytes (Th2). Herein, we first provide evidence that mice immunized at birth against a single MHC class II alloantigen develop pathological features mimicking this variant of the hypereosinophilic syndrome. Indeed, C57BL / 6 mice injected at birth with (C57BL/ 6 x bm12)F1 spleen cells displayed T lymphocytes producing high levels of IL-5 and IL-13, increased blood eosinophil counts, eosinophilic infiltrates in various tissues, hyperplasia of lymphoid tissues, as well as serum hyperIgE. Moreover, eotaxin mRNA accumulated in the spleen of these animals. IL-4-deficient mice developed neither expansion of Th2 cells nor pathological changes except splenomegaly. Eotaxin mRNA accumulation was also prevented in these animals. We conclude that neonatal exposure to a single MHC class II alloantigen is sufficient to elicit an IL-4-dependent hypereosinophilic syndrome mimicking the lymphocytic variant of this disorder in humans.
Le Moine
Alain
A
Laboratory of Experimental Immunology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
Flamand
Véronique
V
de Lavareille
Aurore
A
Paulart
Frédéric
F
Buonocore
Sofia
S
Vanderhaeghen
Marie-Line
ML
Nagy
Nathalie
N
Habran
Claude
C
Kiss
Robert
R
Abramowicz
Daniel
D
Goldman
Michel
M
D000818:Animals; D000831:Animals, Newborn; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004195:Disease Models, Animal; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D017681:Hypereosinophilic Syndrome / Q000276:immunology*; D007114:Immunization; D018793:Interleukin-13 / Q000276:immunology* / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D015848:Interleukin-5 / Q000276:immunology* / Q000378:metabolism; D007519:Isoantigens / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D018793:Interleukin-13; D015848:Interleukin-5; D007519:Isoantigens; D015847:Interleukin-4