Continuous control of autoimmune disease by antigen-dependent polyclonal CD4+CD25+ regulatory T cells in the regional lymph node.
Continuous control of autoimmune disease by antigen-dependent polyclonal CD4+CD25+ regulatory T cells in the regional lymph node.
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DOI：
10.1084/jem.20041033
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发表时间：
2005-09-19
期刊：
影响因子：
--
通讯作者：
Tung KS
中科院分区：
文献类型：
--
作者：
Samy ET;Parker LA;Sharp CP;Tung KS
本研究探讨了CD4+CD25+T细胞(T Regs)抑制自身免疫性疾病的抗原依赖性和抗原特异性问题。根据d3tx小鼠自身免疫性卵巢疾病(AOD)和表达Thy1.1标记的多克隆Tregs，我们确定了：(A)受体T细胞抑制的位置，(B)抑制AOD的Tregs的分布，以及(C)雄性和雌性Tregs的相对疗效。受体CD4+T细胞的扩增、激活/记忆标记物的表达和干扰素-γ的产生在卵巢引流的淋巴结中持续受到抑制，但在其他地方没有。当Thy1.1+T reg耗尽时，细胞的变化被逆转，出现了强大的致病T细胞和严重的AOD。在自身免疫性泪腺炎和自身免疫性前列腺炎抑制期间，区域LNS也有类似的变化。尽管输注的Thy1.1+T细胞调节器在外周淋巴器官中增殖和扩散，但只有从卵巢引流的淋巴系统中提取的调节器在次佳细胞剂量下过继抑制AOD。通过剥夺d3tx受体的卵巢抗原，我们揭示了在抑制AOD方面，暴露于卵巢抗原的女性在抑制AOD方面的优势。因此，多克隆T调节器对疾病的抑制依赖于内源性抗原刺激；这发生在有效的抗原特异性T调节器积聚并持续否定致病T细胞反应的位置。
This study investigated the unresolved issue of antigen-dependency and antigen-specificity of autoimmune disease suppression by CD4+CD25+ T cells (T regs). Based on autoimmune ovarian disease (AOD) in day 3 thymectomized (d3tx) mice and polyclonal T regs expressing the Thy1.1 marker, we determined: (a) the location of recipient T cell suppression, (b) the distribution of AOD-suppressing T regs, and (c) the relative efficacy of male versus female T regs. Expansion of recipient CD4+ T cells, activation/memory marker expression, and IFN-γ production were inhibited persistently in the ovary-draining LNs but not elsewhere. The cellular changes were reversed upon Thy1.1+ T reg depletion, with emergence of potent pathogenic T cells and severe AOD. Similar changes were detected in the regional LNs during autoimmune dacryoadenitis and autoimmune prostatitis suppression. Although the infused Thy1.1+ T regs proliferated and were disseminated in peripheral lymphoid organs, only those retrieved from ovary-draining LNs adoptively suppressed AOD at a suboptimal cell dose. By depriving d3tx recipients of ovarian antigens, we unmasked the supremacy of ovarian antigen-exposed female over male T regs in AOD suppression. Thus, disease suppression by polyclonal T regs depends on endogenous antigen stimulation; this occurs in a location where potent antigen-specific T regs accumulate and continuously negate pathogenic T cell response.
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影响因子：
15.3
作者：
Apostolou, I;von Boehmer, H
通讯作者：
von Boehmer, H
影响因子：
4.4
作者：
Garza, KM;Agersborg, SS;Tung, KSK
通讯作者：
Tung, KSK
调节性T细胞在类风湿关节炎和抗TNFALPHA治疗中的逆转功能受损。
影响因子：
15.3
作者：
Ehrenstein, MR;Evans, JG;Singh, A;Moore, S;Warnes, G;Isenberg, DA;Mauri, C
通讯作者：
Mauri, C
DOI：
10.1084/jem.20020394
发表时间：
2002-07-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jonuleit H;Schmitt E;Kakirman H;Stassen M;Knop J;Enk AH
通讯作者：
Enk AH
影响因子：
3.9
作者：
Hussain, SF;Paterson, Y
通讯作者：
Paterson, Y