期刊
JOURNAL OF IMMUNOLOGY
卷 200, 期 9, 页码 3087-3099出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1701179
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资金
- National Institutes of Health [R01 AI058150]
- Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health
Mouse models of lupus have shown that multiple immune cell types contribute to autoimmune disease. This study sought to investigate the involvement of B cells and dendritic cells in supporting the expansion of inflammatory and regulatory CD4(+) T cells that are critical for lupus pathogenesis. We used lupus-prone B6.NZM2410.Sle1.Sle2.Sle3 (TC) and congenic C57BL/6J (B6) control mice to investigate how the genetic predisposition of these two cell types controls the activity of normal B6 T cells. Using an allogeneic in vitro assay, we showed that TC B1-a and conventional B cells expanded Th17 cells significantly more than their B6 counterparts. This expansion was dependent on CD86 and IL-6 expression and mapped to the Sle1 lupus-susceptibility locus. In vivo, TC B cells promoted greater differentiation of CD4(+) T cells into Th1 and follicular helper T cells than did B6 B cells, but they limited the expansion of Foxp3 regulatory CD4(+) T cells to a greater extent than did B6 B cells. Finally, when normal B6 CD4(+) T cells were introduced into Rag1(-/)-mice, TC myeloid/stromal cells caused their heightened activation, decreased Foxp3 regulatory CD4(+) T cell differentiation, and increased renal infiltration of Th1 and Th17 cells in comparison with B6 myeloid/stromal cells. The results show that B cells from lupus mice amplify inflammatory CD4(+) T cells in a nonredundant manner with myeloid/stromal cells.
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