T cell and B Cell immunity can be reconstituted with mismatched hematopoietic stem cell transplantation without alkylator therapy in artemis-deficient mice using anti-natural killer cell antibody and photochemically treated sensitized donor T cells.
T cell and B Cell immunity can be reconstituted with mismatched hematopoietic stem cell transplantation without alkylator therapy in artemis-deficient mice using anti-natural killer cell antibody and photochemically treated sensitized donor T cells.
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DOI：
10.1016/j.bbmt.2011.10.017
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发表时间：
2012-02
影响因子：
4.3
通讯作者：
Cowan, Morton J.
中科院分区：
文献类型：
--
作者：
Xiao, Tony Z.;Singh, Kona;Dunn, Elizabeth;Ramachandran, Rageshree;Cowan, Morton J.
关键词：
患有Artemis-deficient T-B-NK+ SCID （SCIDA）的儿童有很高的NK细胞排斥反应的风险，并且对用于错配造血干细胞移植（HSCT）的烷基化剂的敏感性增加而产生毒性。我们评估了在artemis缺陷（mArt-/-） C57Bl/6 （B6）小鼠造血干细胞移植前使用非烷基化剂方案，以打开骨髓龛并实现长期多系移植，并实现充分的T和B细胞免疫重建。我们发现，使用抗nk1.1单克隆抗体部分消耗受体NK细胞和供体T细胞对受体脾细胞敏感是必要的。BALB/c敏化T细胞（STC）经补骨脂素和UVA光光化学处理（PCT）抑制增殖，降低移植物抗宿主病（GvHD）和靶宿主造血干细胞（HSC）的风险。4×105 PCT STC与1×105谱系缺失c-kit+ BALB/c HSC共注射，供体T细胞CD4+ 43.9±3.3%,CD8+ 10.9±1.2%；移植后6个月，脾脏和骨髓中供体B220+ IgM+细胞的比例分别为29±7.8%和21.7±4.0，骨髓中供体gran1 +细胞的比例分别为15.0±3.6%，而未接受PCT STC的对照组分别为0.02±0.0.01%、0.13±0.10%、0.53±0.16%、0.49±0.09%和0.20±0.06%。我们发现STC靶向宿主HSC，并且PCT STC在输注后仅24小时内即可检测到，而非光化学处理的STC则会增殖导致致命的GvHD。在接受4-6×105 PCT-STC的组中，死亡率的增加与GvHD的证据有关，特别是6×105细胞的受体。这些结果表明，阻断NK细胞介导的抵抗和在骨髓中制造壁龛对于实现错配供体细胞的多系植入和T细胞和B细胞的重建都是必不可少的，尽管GvHD并没有完全消除。
Children with Artemis-deficient T-B-NK+ SCID (SCIDA) have very high risks of graft rejection from NK cells and toxicity from increased sensitivity to alkylating agents used for mismatched hematopoietic stem cell transplantation (HSCT). We evaluated the use of a non-alkylating agent regimen prior to HSCT in Artemis-deficient (mArt-/-) C57Bl/6 (B6) mice to open marrow niches and achieve long-term multilineage engraftment with full T and B cell immune reconstitution. We found that both partial depletion of recipient NK cells using anti-NK1.1 monoclonal antibody and donor T cells sensitized to recipient splenocytes were necessary. BALB/c sensitized T cells (STC) were photochemically -treated (PCT) with psoralen and UVA light to inhibit proliferation, reduce the risk of Graft-versus-host disease (GvHD) and target host hematopoietic stem cells (HSC). 4×105 PCT STC co-injected with 1×105 lineage-depleted c-kit+ BALB/c HSC resulted in 43.9±3.3% CD4+, 10.9±1.2% CD8+ donor T cells in blood; 29±7.8% and 21.7±4.0 donor B220+ IgM+ in spleen and bone marrow and 15.0±3.6% donor Gran-1+ cells in bone marrow at six months post transplant versus 0.02±0.0.01%, 0.13±0.10%, 0.53±0.16%, 0.49±0.09% and 0.20±0.06%, respectively, in controls that did not receive PCT STC. We found that STC target host HSC, and that PCT STC are detectable up to only 24 hours following infusion in contrast to non-photochemically treated STC which proliferate resulting in fatal GvHD. Increased mortality in the groups receiving 4-6×105 PCT-STC was associated with evidence of GvHD in particular the recipients of 6×105 cells. These results show that blocking NK cell mediated resistance and making niches in bone marrow are both essential to achieve multilineage engraftment of mismatched donor cells and T and B cell reconstitution although GvHD is not completely eliminated.
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影响因子：
20.3
作者：
Aguila, HL;Weissman, IL
通讯作者：
Weissman, IL
影响因子：
20.3
作者：
Sarzotti-Kelsoe, Marcella;Win, Chan M.;Buckley, Rebecca H.
通讯作者：
Buckley, Rebecca H.
影响因子：
20.3
作者：
BLAZAR, BR;TAYLOR, PA;VALLERA, DA
通讯作者：
VALLERA, DA
DOI：
10.1073/pnas.0914865107
发表时间：
2010-02-16
影响因子：
11.1
作者：
Rucci, Francesca;Notarangelo, Luigi D.;Yan, Catherine T.
通讯作者：
Yan, Catherine T.
影响因子：
14.2
作者：
Griffith, Linda M.;Cowan, Morton J.;Shearer, William T.
通讯作者：
Shearer, William T.