Dominant trait linked to chromosome 1 in DBA/2 mice for the resistance to autoimmune gastritis appears in bone marrow cells.
Neonatal thymectomy (NTx) induces autoimmune gastritis (AIG) in BALB/c mice, a model for human type A chronic atrophic gastritis, but not in DBA/2 mice and rarely in CDF1 mice (a hybrid of BALB/c and DBA/2 mice). The aim of this study was to clarify the mechanisms of AIG-resistance in mice bearing the dominant trait of DBA/2. Linkage groups associated with, and cells related to AIG resistance were examined with CDF1-BALB/c backcrosses. Intracellular staining and flow-cytometric bead array for several cytokines were performed on NTx BALB/c mice and NTx DBA/2-chimeric BALB/c mice receiving DBA/2-bone marrow cells. In NTx BALB/c mice, IFN-γ-secreting CD4(+) T cells were increased, but not in NTx DBA/2 mice. Because Vβ6(+) T cell-bearing mice of half of their backcrosses developed AIG, but the other half of Vβ6(+) T cell-negative mice developed scarcely, resistance for AIG generation is associated with the presence of the Mls-1a locus on chromosome 1 in DBA/2 mice, which deletes Vβ6(+) T cells. NTx DBA/2-chimera BALB/c mice showed dominant production of IL-10 and resistance for AIG, although the deletion of Vβ6(+) T cells was found not to be a cause of AIG-resistance from Mls-1a locus segregation experiments. Although NTx DBA/2-chimeric BALB/c mice did not suffer from AIG, they brought immediate precursors of T cells for AIG. It is concluded that DBA/2 mice generate bone marrow-derived cells that produce anti-inflammatory cytokines to prevent the activation of AIG-T cells.
Laboratory of Immunobiology, Department of Life Sciences, Graduate School of Science and Technology, Niigata University, 8050 Ikarashi-2-no-cho, Nishi-ku, Niigata 950-2181, Japan.
Masato
M
Fujii
Kenji
K
Suzuki
Satoru
S
Suenaga
Mariko
M
Wakatsuki
Yoshihiro
Y
Kushida
Maki
M
Touma
Masamichi
M
Hosono
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002678:Chimera / Q000235:genetics; D033481:Chromosomes, Mammalian / Q000235:genetics*; D016207:Cytokines / Q000378:metabolism / Q000502:physiology; D004195:Disease Models, Animal; D060467:Disease Resistance / Q000235:genetics; D005260:Female; D005756:Gastritis / Q000235:genetics* / Q000276:immunology*; D005799:Genes, Dominant / Q000235:genetics*; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines