Injection of bleomycin in newborn mice induces autoimmune sialitis that is transferred by CD4 T cells.
Bleomycin (BLM) induces cellular apoptosis or necrosis by producing reactive oxygen species, and has been used to induce scleroderma in adult mice. We wondered whether BLM induces the same pathological phenotype in newborn mice as in adult mice. BLM was subcutaneously administrated to newborn BALB/c mice. At 1 month of age, BLM-treated mice showed severe destruction of salivary glands with enlargement of nearby lymph nodes. These nodes contained CD4(+) T cells and B220(+)cells with high expression of MHC class II molecules. In addition, autoantibodies were detected by HEp-2 staining and western blotting. The cell transfer experiments were performed to evaluate the role of autoimmune phenomena in these pathological changes. Following the transfer of enriched CD4(+) T cells to 1-month-old BALB/c nude mice, the salivary glands were severely damaged with CD4(+) T cell and B220(+) cells infiltrations. The number of T-cell antigen receptor Vbeta 8.3(+) CD4(+) T cells was significantly increased in BLM-treated murine spleen. These findings will provide new insights into the causal factors of environment in autoimmunity and the relationship between autoreactive CD4(+) T cells and autoantibodies.
Ishikawa
Hideaki
H
Department of Immunology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Aichi, Japan.
Ito
Sachiko
S
Nishio
Naomi
N
Yuzawa
Yukio
Y
Matsuo
Sei-Ichi
S
Isobe
Ken-Ichi
K
D019264:Adoptive Transfer; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D015551:Autoimmunity / Q000276:immunology; D001761:Bleomycin / Q000008:administration & dosage / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D055104:Infusions, Subcutaneous; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012469:Salivary Glands / Q000276:immunology / Q000473:pathology; D012793:Sialadenitis / Q000276:immunology* / Q000473:pathology
D000903:Antibiotics, Antineoplastic; D001323:Autoantibodies; D001761:Bleomycin