Lethal host-versus-graft disease and hypereosinophilia in the absence of MHC I–T-cell interactions
Jérôme D. Coudert, Gilles Foucras, Cécile Demur, Christiane Coureau, Catherine Mazerolles, Georges Delsol, Philippe Druet, Jean-Charles Guéry
Jérôme D. Coudert, Gilles Foucras, Cécile Demur, Christiane Coureau, Catherine Mazerolles, Georges Delsol, Philippe Druet, Jean-Charles Guéry
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Article

Lethal host-versus-graft disease and hypereosinophilia in the absence of MHC I–T-cell interactions

Abstract

Neonatal injection of semiallogeneic spleen cells in BALB/c mice induces a self-limited state of chimerism that promotes the differentiation of donor-specific CD4 T cells toward the Th2 phenotype. Here we show that injection of spleen cells from β2-microglobulin–deficient (BALB/c × C57BL/6) F1 mice into BALB/c newborns with a disrupted β2-microglobulin (β2m) gene results in a lethal lymphoproliferative disorder associated with uncontrolled Th2 response, long-term persistence of donor B cells, and sustained blood eosinophilia. Autoimmune manifestations are also enhanced and characterized by a severe autoantibody-mediated glomerulonephritis. Histological examination of the spleen shows a hyperplasia of periarteriolar lymphoid sheaths, with accumulation of eosinophils and basophils, and variable degree of fibrosis. Perivascular lymphoid infiltrates with eosinophils are also found in the lung and are correlated with disease severity. Such abnormalities are almost absent using β2m-sufficient mice. These data demonstrate that induction of lymphoid chimerism in the absence of MHC class I–T-cell interactions results in a lethal form of host-versus-graft disease that represents a unique model of Th2-dependent chronic inflammatory disease associated with an hypereosinophilic syndrome in mice.

Authors

Jérôme D. Coudert, Gilles Foucras, Cécile Demur, Christiane Coureau, Catherine Mazerolles, Georges Delsol, Philippe Druet, Jean-Charles Guéry

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Persistence of IgE production, high mortality rate, and increased incide...
Persistence of IgE production, high mortality rate, and increased incidence of albuminuria in β2m° BALB/c mice injected at birth with β2m° CB6F1 splenocytes. Normal (a) and β2m° (b) BALB/c mice were injected at birth with 50 × 106 CB6F1 spleen cells from normal or β2m° donors, respectively. Mice were bled at 4–16 weeks of age and IgE were quantified in individual mice serum by ELISA. Statistically significant decrease of IgE concentration was compared between the 8-, 10-, 12-, and 16-week values and the 4-week values. Bars represent means of individual mice. (c) Mortality of neonatally injected β2m° (solid line; n = 9) and WT mice (dotted line; n = 13) was followed up until the age of 22 weeks. (d) Albumin was quantified in urine by ELISA at 10–16 weeks of age. Mice were considered albuminuric when albumin titer was greater than 15 μg/mL. Statistical analyses were performed as indicated in Methods. AP < 0.001; BP < 0.01.