Profound depletion of host conventional dendritic cells, plasmacytoid dendritic cells, and B cells does not prevent graft-versus-host disease induction.
Profound depletion of host conventional dendritic cells, plasmacytoid dendritic cells, and B cells does not prevent graft-versus-host disease induction.
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DOI：
10.4049/jimmunol.1102795
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发表时间：
2012-04-15
期刊：
影响因子：
--
通讯作者：
Shlomchik WD
中科院分区：
文献类型：
--
作者：
Li H;Demetris AJ;McNiff J;Matte-Martone C;Tan HS;Rothstein DM;Lakkis FG;Shlomchik WD
alloSCT的疗效受到移植物抗宿主病（GVHD）的限制。宿主造血抗原提呈细胞（APC）是GVHD的重要启动者，使其成为GVHD预防的逻辑靶点。传统的树突状细胞（cDC）是T细胞免疫的其他模型中T细胞应答的关键APC，并且它们足以诱导GVHD。然而，我们在这里报告在两个多克隆GVHD模型中，其中宿主造血APC是必不可少的，当受体cDC被诱导或组成性删除时，GVHD没有减少。另外的浆细胞样DC和B细胞的深度消耗，伴随或不伴随CD 11 B+细胞的部分消耗，也没有改善GVHD。这些数据表明，与病原体模型相反，关于哪些宿主细胞可以引发GVHD存在令人惊讶的冗余。或者，非常低数量的靶向APC就足够了。我们假设病原体和GVHD模型中APC需求的差异与靶抗原的可用性有关。在抗病原体反应中，专门的APC被独特地装备以获得和呈递外源抗原，而在GVHD中，所有宿主细胞直接呈递同种异体抗原。这些研究使得基于试剂的宿主APC耗竭不太可能在临床上预防GVHD。
The efficacy of alloSCT is limited by graft-versus-host disease (GVHD). Host hematopoietic antigen presenting cells (APCs) are important initiators of GVHD making them logical targets for GVHD prevention. Conventional dendritic cells (cDCs) are key APCs for T cell responses in other models of T cell immunity and they are sufficient for GVHD induction. However, we report here in two polyclonal GVHD models in which host hematopoietic APCs are essential, that GVHD was not decreased when recipient cDCs were inducibly or constitutively deleted. Additional profound depletion of plasmacytoid DCs and B cells, with or without partial depletion of CD11b+ cells, also did not ameliorate GVHD. These data indicate that, in contrast to pathogen models, there is a surprising redundancy as to which host cells can initiate GVHD. Alternatively, very low numbers of targeted APCs were sufficient. We hypothesize the difference in APC requirements in pathogen and GVHD models relates to the availability of target antigens. In anti-pathogen responses specialized APCs are uniquely equipped to acquire and present exogenous antigens whereas in GVHD all host cells directly present alloantigens. These studies make it unlikely that reagent-based host APC depletion will prevent GVHD in the clinic.
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影响因子：
32.4
作者：
Jung, S;Unutmaz, D;Lang, RA
通讯作者：
Lang, RA
影响因子：
4.4
作者：
Probst, HC;van den Broek, M
通讯作者：
van den Broek, M
DOI：
10.1084/jem.20062648
发表时间：
2007-07-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Caton ML;Smith-Raska MR;Reizis B
通讯作者：
Reizis B
影响因子：
15.9
作者：
Menke, Julia;Iwata, Yasunori;Kelley, Vicki R.
通讯作者：
Kelley, Vicki R.
影响因子：
5.4
作者：
Murillo, Oihana;Dubrot, Juan;Melero, Ignacio
通讯作者：
Melero, Ignacio