CD4 T cells mediate cardiac xenograft rejection via host MHC Class II.
CD4 T cells mediate cardiac xenograft rejection via host MHC Class II.
复制标题
DOI：
10.1016/j.healun.2012.05.018
复制
发表时间：
2012-09
期刊：
影响因子：
--
通讯作者：
Pietra BA
中科院分区：
文献类型：
--
作者：
Plenter RJ;Grazia TJ;Doan AN;Gill RG;Pietra BA
先前的研究表明，急性CD 4 T细胞介导的心脏移植排斥反应需要供体MHC II类表达，并且可以独立于“间接”抗原呈递。然而，其他研究表明，间接抗原呈递给CD 4 T细胞可能在细胞异种移植免疫中发挥主要作用。因此，直接/间接CD 4 T细胞反应性对心脏异种移植物的相对作用尚不清楚。我们着手确定间接CD 4 T细胞反应性在心脏异种移植排斥反应中的作用。将大鼠心脏异位移植到野生型和免疫缺陷小鼠体内。接受者未经处理，用耗尽抗体处理或用野生型细胞重建。抗体耗竭证实C57 Bl/6小鼠中的大鼠心脏异种移植排斥是CD 4 T细胞依赖性的。此外，心脏异种移植物在B6 MHC II类（C2 D）缺陷小鼠中长期存活。C2 D小鼠中的移植物接受不是继发于单独的CD 4 T细胞缺乏，因为转移的B6 CD 4 T细胞未能在C2 D宿主中引发排斥反应。此外，纯化的CD 4 T细胞足以用于免疫缺陷B6 rag 1 −/−受体的大鼠心脏异种移植物的急性排斥反应。重要的是，CD 4 T细胞在C2 Drag 1 −/−宿主中没有排斥大鼠心脏，与心脏同种异体移植的结果形成对比。“直接”异种反应性CD 4 T细胞不足以介导排斥反应，尽管在体外对大鼠刺激细胞具有强烈的反应性。总之，结果表明，CD 4 T细胞是必要的和足够的急性心脏异种移植排斥反应和宿主MHC II类在这个过程中是至关重要的。
Previous studies indicate that acute CD4 T-cell-mediated cardiac allograft rejection requires donor MHC class II expression and can be independent of ‘indirect’ antigen presentation. However, other studies suggest that indirect antigen presentation to CD4 T-cells may play a primary role in cellular xenograft immunity. Thus, the relative roles of direct/indirect CD4 T-cell reactivity against cardiac xenografts is unclear. We set out to determine the role for indirect CD4 T-cell reactivity in cardiac xenograft rejection. Rat hearts were transplanted heterotopically into wild-type and immuno-deficient mice. Recipients were untreated, treated with depleting antibodies or reconstituted with wild-type cells. Antibody depletion confirmed that rat heart xenograft rejection in C57Bl/6 mice was CD4 T-cell-dependent. Also, heart xenografts survived long-term in B6 MHC class II (C2D) deficient mice. Graft acceptance in C2D mice was not secondary to CD4 T-cell deficiency alone, because transferred B6 CD4 T-cells failed to trigger rejection in C2D hosts. Furthermore, purified CD4 T-cells were sufficient for acute rejection of rat heart xenografts in immune-deficient B6rag1−/− recipients. Importantly, CD4 T-cells did not reject rat hearts in C2Drag1−/− hosts, contrasting results using cardiac allografts. ‘Direct’ xenoreactive CD4 T-cells were not sufficient to mediate rejection despite vigorous reactivity to rat stimulator cells in vitro. Taken together, results show that CD4 T-cells are both necessary and sufficient for acute cardiac xenograft rejection and host MHC class II is critical in this process.
登录
查看更多内容
影响因子：
56.9
作者：
GRUSBY, MJ;JOHNSON, RS;GLIMCHER, LH
通讯作者：
GLIMCHER, LH
影响因子：
4.4
作者：
Kupfer, TM;Crawford, ML;Gill, RG
通讯作者：
Gill, RG
DOI：
10.1089/clo.2004.6.327
发表时间：
2004-12-01
期刊：
CLONING AND STEM CELLS
影响因子：
--
作者：
Harrison, S;Boquest, A;Nottle, M
通讯作者：
Nottle, M
影响因子：
8.9
作者：
Gonzalez-Stawinski, Gonzalo V.;Davis, R. Duane, Jr.
通讯作者：
Davis, R. Duane, Jr.
影响因子：
6.2
作者：
CORRY, RJ;WINN, HJ;RUSSELL, PS
通讯作者：
RUSSELL, PS