Tissue-specific expansion of NKT and CD5+B cells at the onset of autoimmune disease in (NZBxNZW)F1 mice.
Natural killer T (NKT) cells and CD5(+)B cells were searched for in various immune organs of autoimmune prone (NZBxNZW)F(1) (NZB/W F(1)) mice. The number of lymphocytes increased in the liver, spleen, and peritoneal cavity after the onset of disease (at the age of 30 weeks) while the number of thymocytes decreased at that time. Prominent changes of lymphocyte subsets were seen in the liver and peritoneal cavity, namely, expansion of IL-2Rbeta(+)TCRalpha beta(int) cells in the liver and of CD5(+)B220(+) cells in the peritoneal cavity. The majority of TCRalpha beta(int) cells in the liver were NK1.1(+), and CD5(+)B cells in the peritoneal cavity were CD1d(+). Proteinuria became prominent in NZB/W F(1) mice with the progression of disease. In parallel with this progression, the proportion of NKT cells decreased slightly in the liver, but their absolute number remained at a high level in this organ. These NKT cells were CD4(+) and used an invariant chain of Valpha14Jalpha281 for TCRalpha. Reflecting the elevation of CD5(+)B cells, autoantibodies against hepatocyte cytoplasmand denatured DNA were detected in sera. Although NKT cells are known to be immunoregulatory cells in some autoimmune mice, the present results raise the possibility that NKT cells as well as CD5(+)B cells might be associated with the onset of autoimmune diseases in NZB/W F(1) mice. Indeed, NKT cells in F(1) mice had a high potential to induce autoimmune-like inflammationwhen alpha-galactosylceramide was administered or when active NKT cells were transferred into young F(1) mice.
Department of Immunology, Niigata University School of Medicine, Japan.
Sufi Reza M
SR
Morshed
Kaiissar
K
Mannoor
Ramesh C
RC
Halder
Hiroki
H
Kawamura
Makoto
M
Bannai
Hiroho
H
Sekikawa
Hisami
H
Watanabe
Toru
T
Abo
D019264:Adoptive Transfer; D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D000918:Antibody Specificity; D018949:Antigens, CD1 / Q000032:analysis; D055610:Antigens, CD1d; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D015704:CD4 Antigens / Q000032:analysis*; D018956:CD5 Antigens / Q000032:analysis*; D003433:Crosses, Genetic; D003593:Cytoplasm / Q000276:immunology; D004247:DNA / Q000276:immunology; D018450:Disease Progression; D005699:Galactosylceramides / Q000276:immunology / Q000633:toxicity; D022781:Hepatocytes / Q000276:immunology; D007678:Kidney Glomerulus / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008099:Liver / Q000473:pathology; D018655:Lymphocyte Count; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008814:Mice, Inbred NZB; D010529:Peritoneal Cavity / Q000473:pathology; D011507:Proteinuria / Q000209:etiology / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology / Q000637:transplantation
D000974:Antibodies, Antinuclear; D018949:Antigens, CD1; D055610:Antigens, CD1d; D001323:Autoantibodies; D015704:CD4 Antigens; D018956:CD5 Antigens; D005699:Galactosylceramides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004247:DNA