An immunomodulatory role for Follistatin-like 1 in heart allograft transplantation
An immunomodulatory role for Follistatin-like 1 in heart allograft transplantation
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DOI：
10.1111/j.1600-6143.2008.02398.x
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发表时间：
2008-11-01
影响因子：
8.8
通讯作者：
Cuturi, M. -C.
中科院分区：
文献类型：
--
作者：
Le Luduec, J. B.;Condamine, T.;Cuturi, M. -C.
供体特异性输血（DST）可使大鼠心脏移植耐受。我们以前曾报道过这种耐受性与强烈的白细胞浸润有关，并且需要宿主CD8（+）T细胞和TGF β。为了鉴定参与耐受诱导阶段的新分子，我们比较了移植后5天耐受和排斥的心脏同种异体移植物（抑制性消减杂交）。我们确定了卵泡抑素样1（FSTL 1）转录的过度表达在耐受的同种异体移植物相比，排斥的同种异体移植物或同基因移植物。我们发现，FSTL 1是过表达的诱导和维持阶段的耐受性，并出现特定的耐受性模型诱导的DST。移植物浸润细胞的分析显示，FSTL 1在耐受移植物的CD8（+）T细胞中的主要表达，移植前这些细胞的耗竭废除了FSTL 1表达和心脏移植物存活。此外，通过体内腺病毒基因转移过表达FSTL 1显著延长了与抑制促炎细胞因子IL 6、IL 17 A和IFN γ相关的同种异体移植物存活。综上所述，这些结果表明，FSTL 1可能是介导心脏移植耐受机制的活性成分。
Donor-specific tolerance to heart allografts in the rat can be achieved by donor-specific blood transfusions (DST) before transplantation. We have previously reported that this tolerance is associated with strong leukocyte infiltration, and that host CD8(+) T cells and TGF beta are required. In order to identify new molecules involved in the induction phase of tolerance, we compared tolerated and rejected heart allografts (suppressive subtractive hybridization) 5 days after transplantation. We identified overexpression of Follistatin-like 1 (FSTL1) transcript in tolerated allografts compared to rejected allografts or syngeneic grafts. We show that FSTL1 is overexpressed during both the induction and maintenance phase of tolerance, and appears to be specific to the tolerance model induced by DST. Analysis of graft-infiltrating cells revealed predominant expression of FSTL1 in CD8(+) T cells from tolerated grafts, and depletion of these cells prior to transplantation abrogated FSTL1 expression and heart allograft survival. Moreover, overexpression of FSTL1 by adenovirus gene transfer in vivo significantly prolonged allograft survival in association with inhibition of the proinflammatory cytokines, IL6, IL17 A and IFN gamma. Taken together, these results suggest that FSTL1 could be an active component of the mechanisms mediating heart allograft tolerance.