Lethal host-versus-graft disease and hypereosinophilia in the absence of MHC I-T-cell interactions.
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 beta2-microglobulin-deficient (BALB/c x C57BL/6) F1 mice into BALB/c newborns with a disrupted beta2-microglobulin (beta2m) 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 beta2m-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.
Coudert
J D
JD
Institut National de la Santé et de la Recherche Médicale (INSERM) U28, Institut Fédératif de Recherche 30, and Université Paul Sabatier, Toulouse, France.
Foucras
G
G
Demur
C
C
Coureau
C
C
Mazerolles
C
C
Delsol
G
G
Druet
P
P
Guéry
J C
JC
D000818:Animals; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006789:Host vs Graft Reaction / Q000276:immunology*; D017681:Hypereosinophilic Syndrome / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018418:Th2 Cells / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000235:genetics / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin