Human double-negative T cells in systemic lupus erythematosus provide help for IgG and are restricted by CD1c
Human double-negative T cells in systemic lupus erythematosus provide help for IgG and are restricted by CD1c
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DOI：
10.4049/jimmunol.165.9.5338
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发表时间：
2000-11-01
影响因子：
4.4
通讯作者：
Hahn, BH
中科院分区：
文献类型：
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作者：
Sieling, PA;Porcelli, SA;Hahn, BH
为了了解T细胞帮助系统性红斑狼疮（SLE）产生IBG的机制，我们研究了CD4-和cd8阴性（双阴性（DN）） T细胞的反应，因为：1)DN T细胞在SLE患者中存在异常高的频率，并且可以诱导。致病性自身抗体;2) DN T细胞库包括受CD1 ag呈递分子限制的细胞；3) CD1c在循环B细胞群上表达。我们从SLE患者和健康个体中获得了DN T细胞系。在CD1(+) APCs存在的情况下，来自SLE患者的DN T细胞系产生IL-4和ifn - γ，而来自健康供体的DN T细胞产生ifn - γ，但不产生IL-4。通常，来自高活性疾病患者的细胞产生高水平的ifn - γ；来自低活性细胞的细胞产生高IL-4，来自健康供体的CD1c-直接反应T细胞与CD1c(+) B细胞共培养可诱导IgM抗体，但很少或没有IgG。相反，来自SLE患者的CD1c-直接反应T细胞诱导同型转换，IgG产生显著增加。CD1c中和抗体抑制了DN T细胞诱导CD1c(+) B细胞产生IgG的能力，进一步表明CD1c介导了T细胞和B细胞的相互作用。抗体对IL-4的中和也抑制了IgG的产生，这与来自这些患者的TPN T细胞的细胞因子模式相关。这些数据表明，来自SLE患者的CD1c限制性T细胞可以帮助CD1c(+) B细胞产生IgG，因此可以促进SLE的致病性自身抗体反应。
To understand the mechanism of T cell help for IBG production in systemic lupus erythematosus (SLE) we investigated the response of CD4- and CD8-negative (double-negative (DN)) T cells because: 1) DN T cells are present at unusually high frequency in patients with SLE and can induce. pathogenic autoantibodies; 2) the DN T cell repertoire includes cells restricted by CD1 Ag-presenting molecules; and 3) CD1c is expressed on a population of circulating B cells. We derived DN T cell lines from SLE patients and healthy individuals. In the presence of CD1(+) APCs, DN T cell lines from SLE patients produced both IL-4 and IFN-gamma, whereas DN T cells from healthy donors produced IFN-gamma, but no IL-4, In general, cells from patients with highly active disease produced high levels of IFN-gamma; cells from those with little activity produced high IL-4, Coculture of CD1c-directly reactive T cells from healthy donors with CD1c(+) B cells elicited IgM Abs, but little or no IgG, In contrast, CD1c-directly reactive T cells from SLE patients induced isotype switching, with a striking increase in IgG production. Neutralizing Abs to CD1c inhibited the ability of DN T cells to induce IgG production from CD1c(+) B cells, further indicating that CD1c mediated the T and B cell interaction. IgG production was also inhibited by neutralizing Abs to IL-4, correlating with the cytokine pattern of TPN T cells derived from these patients. The data suggest that CD1c-restricted T cells from SLE patients can provide help to CD1c(+) B cells for IgG production and could therefore promote pathogenic autoantibody responses in SLE.