The role of CD4CD25 T cells in autoantibody production in murine lupus.
Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease characterized by the loss of tolerance to self-antigen. Because it is currently not known if regulatory T (T(reg)) cells are involved in the pathogenesis, we determined the frequency of CD4(+)CD25(+) T cells and assayed the related gene expression levels in CD4(+)CD25(+) T cells isolated from both lupus mice (NZB/NZW F(1)) and normal control mice (DBA2/NZW F(1)). The results showed that the frequency of CD4(+)CD25(+) T cells in lupus mice was lower than that of normal mice. Except for the high expression level of interleukin (IL)-10 mRNA, CD4(+)CD25(+) T cells from lupus mice expressed normal forkhead box P3 (Foxp3) and transforming growth factor (TGF)-beta mRNA, and exerted suppressive functions. Furthermore, we depleted CD25(+) T(reg) cells of non-autoimmune mice with anti-CD25 antibody and broke their tolerance with apoptotic cell-pulsed dendritic cells for the follow-up of autoantibody levels. The mice in the CD25(+) cell-depleted group had higher titres of anti-double-strand/single-strand DNA antibodies than those of the isotype control antibody-treated group. These findings indicated that CD4(+)CD25(+) T cells might be involved in the regulatory mechanism of autoantibody production.
Hsu
W-T
WT
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.
Suen
J-L
JL
Chiang
B-L
BL
D000818:Animals; D017209:Apoptosis; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics; D015870:Gene Expression; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008814:Mice, Inbred NZB; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics
D001323:Autoantibodies; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta; D016753:Interleukin-10