An unexpected counter-regulatory role of IL-10 in B-lymphocyte-mediated transplantation tolerance.
An unexpected counter-regulatory role of IL-10 in B-lymphocyte-mediated transplantation tolerance.
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DOI：
10.1111/j.1600-6143.2010.03027.x
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发表时间：
2010-04
期刊：
影响因子：
--
通讯作者：
Deng S
中科院分区：
文献类型：
--
作者：
Zhao G;Moore DJ;Lee KM;Kim JI;Duff PE;O'Connor MR;Hirohashi T;Lei J;Yang M;Markmann JF;Deng S
抗CD 45 RB蛋白单克隆抗体诱导多种类型同种异体移植耐受的研究我们先前已经确定，这种耐受方案依赖于B淋巴细胞的调节功能来实现其效果。B淋巴细胞也被报道在其他几种情况下参与免疫调节。在大多数这些系统中，B淋巴细胞的调节功能取决于IL-10的产生。因此，我们研究了IL-10在B细胞介导的移植耐受的抗CD 45 RB模型中的作用。令人惊讶的是，使用抗体介导的IL-10中和、IL-10缺陷型受体和IL-10缺陷型B淋巴细胞的过继转移，我们发现IL-10实际上反调节由抗CD 45 RB诱导的耐受性。此外，与单独的抗CD 45 RB相比，IL-10的中和减少了慢性同种异体移植物血管病变的发展，并减少了移植物反应性同种抗体的产生。这些数据表明，调节B淋巴细胞在移植耐受中的参与可能不同于它们在其他系统中的运作方式。鉴定介导移植耐受的特异性B淋巴细胞并确定其作用机制可能会对建立和维持抗原特异性耐受的复杂细胞网络产生新的见解。
Monoclonal antibody against the CD45RB protein induces stable transplantation tolerance to multiple types of allograft. We have previously established that this tolerance protocol relies on the regulatory function of B lymphocytes for its effect. B lymphocytes have also been reported to participate in immune regulation in several other settings. In most of these systems, the regulatory function of B lymphocytes depends on the production of IL-10. Therefore, we investigated the role of IL-10 in the anti-CD45RB model of B-cell-mediated transplantation tolerance. Surprisingly, using antibody-mediated neutralization of IL-10, IL-10-deficient recipients and adoptive transfer of IL-10-deficient B lymphocytes, we found that IL-10 actually counter-regulates tolerance induced by anti-CD45RB. Furthermore, neutralization of IL-10 reduced the development of chronic allograft vasculopathy compared to anti-CD45RB alone and reduced the production of graft reactive alloantibodies. These data suggest that the participation of regulatory B lymphocytes in transplantation tolerance may be distinct from how they operate in other systems. Identifying the specific B lymphocytes that mediate transplantation tolerance and defining their mechanism of action may yield new insights into the complex cellular network through which antigen-specific tolerance is established and maintained.
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影响因子：
4.4
作者：
Deng, Shaoping;Moore, Daniel J.;Markmann, James F.
通讯作者：
Markmann, James F.
影响因子：
6.4
作者：
Ono, S;Shao, DZ;Hamaoka, T
通讯作者：
Hamaoka, T
DOI：
10.1084/jem.186.10.1749
发表时间：
1997-11-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Mizoguchi A;Mizoguchi E;Smith RN;Preffer FI;Bhan AK
通讯作者：
Bhan AK
影响因子：
6.2
作者：
Gareau, Alison;Hirsch, Gregory M.;Nashan, Bjorn
通讯作者：
Nashan, Bjorn
影响因子：
20.3
作者：
Reichardt, Peter;Dornbach, Bastian;Gunzer, Matthias
通讯作者：
Gunzer, Matthias