CD8+ Foxp3+ regulatory T cells are induced during graft-versus-host disease and mitigate disease severity.
CD8+ Foxp3+ regulatory T cells are induced during graft-versus-host disease and mitigate disease severity.
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DOI：
10.4049/jimmunol.1200886
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发表时间：
2012-07-01
期刊：
影响因子：
--
通讯作者：
Drobyski WR
中科院分区：
文献类型：
--
作者：
Beres AJ;Haribhai D;Chadwick AC;Gonyo PJ;Williams CB;Drobyski WR
调节性T细胞（Treg），特别是CD 4 + Foxp 3 + T细胞，已显示在同种异体干细胞移植后维持耐受性中起重要作用。在目前的研究中，我们已经鉴定了在GVHD早期诱导的CD 8 + Foxp 3 + T细胞群体，其构成整个Treg群体的显著百分比，并且存在于所有主要的GVHD靶器官中。这些细胞表达许多与CD 4 + T细胞上发现的相同的细胞表面分子，并有效地抑制体外同种异体反应性T细胞应答。这些细胞的诱导与供体和受体之间MHC差异的程度呈正相关，并且在几乎所有组织部位中均显著大于CD 4+诱导的T细胞（iT细胞）。与能够产生两种iTreg群体的动物相比，缺乏产生CD 8+和CD 4 + iTreg的能力的小鼠具有加速的GVHD死亡率。两种iTreg群体的缺乏与活化供体T细胞的显著更大扩增以及分泌IFN-γ和IL-17的CD 4+和CD 8 + T细胞数量的增加相关。然而，在完全不存在CD 4 + iT细胞的情况下，CD 8 + iT细胞的存在足以防止GVHD死亡率增加，表明至少一种功能性iTreg群体足以防止GVHD严重程度的加重，并且CD 8 + iT细胞可以补偿CD 4 + iT细胞。这些研究定义了一种新的CD 8 + T细胞群，其在减轻同种异体干细胞移植后GVHD的严重程度中发挥作用。
Regulatory T cells (Tregs), in particular CD4+ Foxp3+ T cells, have been shown to play an important role in the maintenance of tolerance after allogeneic stem cell transplantation. In the current study, we have identified a population of CD8+ Foxp3+ T cells that are induced early during GVHD, constitute a significant percentage of the entire Treg population, and are present in all major GVHD target organs. These cells expressed many of the same cell surface molecules as found on CD4+ Tregs and potently suppressed in vitro alloreactive T cell responses. Induction of these cells correlated positively with the degree of MHC disparity between donor and recipient and was significantly greater than that observed for CD4+ induced Tregs (iTregs) in nearly all tissue sites. Mice that lacked the ability to make both CD8+ and CD4+ iTregs had accelerated GVHD mortality compared to animals that were competent to make both iTreg populations. The absence of both iTreg populations was associated with significantly greater expansion of activated donor T cells and increased numbers of CD4+ and CD8+ T cells that secreted IFN-γ and IL-17. The presence of CD8+ iTregs, however, was sufficient to prevent increased GVHD mortality in the complete absence of CD4+ Tregs, indicating at least one functional iTreg population was sufficient to prevent an exacerbation in GVHD severity, and that CD8+ iTregs could compensate for CD4+ iTregs. These studies define a novel population of CD8+ Tregs that play a role in mitigating the severity of GVHD after allogeneic stem cell transplantation.
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影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
32.4
作者：
Haribhai D;Williams JB;Jia S;Nickerson D;Schmitt EG;Edwards B;Ziegelbauer J;Yassai M;Li SH;Relland LM;Wise PM;Chen A;Zheng YQ;Simpson PM;Gorski J;Salzman NH;Hessner MJ;Chatila TA;Williams CB
通讯作者：
Williams CB
影响因子：
82.9
作者：
Korn, Thomas;Reddy, Jayagopala;Kuchroo, Vijay K.
通讯作者：
Kuchroo, Vijay K.
供体型CD4（+）CD25（+）调节性T细胞在同种异体骨髓移植后抑制致命的急性移植物抗宿主疾病。
影响因子：
15.3
作者：
Hoffmann, Petra;Ermann, Joerg;Edinger, Matthias;Fathman, C Garrison;Strober, Samuel
通讯作者：
Strober, Samuel
影响因子：
4.4
作者：
Denning, Timothy L.;Granger, Steve;Kronenberg, Mitchell
通讯作者：
Kronenberg, Mitchell