Efficient and selective prevention of GVHD by antigen-specific induced Tregs via linked-suppression in mice.
Efficient and selective prevention of GVHD by antigen-specific induced Tregs via linked-suppression in mice.
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DOI：
10.1016/j.bbmt.2010.12.710
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发表时间：
2011-03
影响因子：
4.3
通讯作者：
Yu, Xue-Zhong
中科院分区：
文献类型：
--
作者：
Semple, Kenrick;Yu, Yu;Wang, Dapeng;Anasetti, Claudio;Yu, Xue-Zhong
Naturally occurring regulatory T cells (nTregs) suppress the development of GVHD and may spare graft-versus-leukemia (GVL) effect. Because nTreg is a rare population in a healthy individual, the limited source and the non-selective suppression are major hurdles towards the application of nTregs in the control of clinical GVHD after allogeneic HCT. An alternative approach is to generate induced Tregs (iTregs) from naïve CD4 precursors, but the effectiveness of iTregs in the control of GVHD is highly controversial and requires further investigation. The other critical but unsolved issue on Treg therapy is how to achieve antigen (Ag)-specific tolerance that distinguishes GVHD and GVL effect. To address the important issues on the effectiveness of iTregs and Ag-specificity of Tregs, we generated Ag-specific iTregs and tested their potential in the prevention of GVHD in pre-clinical BMT model. CD4+CD25+Foxp3+ iTregs generated from OT-II TCR transgenic T cells specific for OVA target Ag efficiently prevented GVHD induced by polyclonal T effector cells (Teffs) only in the allogeneic recipients that express OVA protein but not in OVA− recipients. The efficacy of these Ag-specific iTregs was significantly higher than polyclonal iTregs. As controls, OT-II CD4+Foxp3− cells had no effect on GVHD development in OVA− recipients and exacerbated GVHD in OVA+ recipients when transplanted together with polyclonal Teffs. Because the iTregs recognize OVA whereas Teffs recognize alloAg bm12, our data reveal for the first time that Tregs prevent GVHD through a linked suppression. Mechanistically, OT-II iTregs expanded extensively, and significantly suppressed expansion and infiltration of Teffs in OVA+ but not in OVA− recipients. These results demonstrate that Ag-specific iTregs can prevent GVHD efficiently and selectively, providing a proof of principle that Ag-specific iTregs may represent a promising cell therapy for their specificity and higher efficacy in allogeneic HCT.
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DOI：
10.4049/jimmunol.181.4.2855
发表时间：
2008-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Golovina TN;Mikheeva T;Suhoski MM;Aqui NA;Tai VC;Shan X;Liu R;Balcarcel RR;Fisher N;Levine BL;Carroll RG;Warner N;Blazar BR;June CH;Riley JL
通讯作者：
Riley JL
影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
4.4
作者：
DiPaolo, Richard J.;Brinster, Carine;Shevach, Ethan M.
通讯作者：
Shevach, Ethan M.
影响因子：
8.8
作者：
Gao, W.;Lu, Y.;Strom, T. B.
通讯作者：
Strom, T. B.
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