Expansion of a restricted residual host T reg-cell repertoire is dependent on IL-2 following experimental autologous hematopoietic stem transplantation.
Expansion of a restricted residual host T reg-cell repertoire is dependent on IL-2 following experimental autologous hematopoietic stem transplantation.
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DOI：
10.1002/eji.201141611
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发表时间：
2011-12
影响因子：
5.4
通讯作者：
Levy, Robert B.
中科院分区：
文献类型：
--
作者：
Bayer, Allison L.;Chirinos, Jackeline;Cabello, Cecilia;Yang, Jing;Matsutani, Takaji;Malek, Thomas R.;Levy, Robert B.
我们之前发现了自体造血干细胞移植（HSCT）后残留的Treg细胞群，在淋巴细胞减少的移植受者体内迅速经历显著扩增，然后由供者重新获得Treg细胞。这些CD4+Foxp3+ T细胞对自身免疫性疾病的发展提供保护。尽管消融条件反射会导致过量的IL-7和IL-15，但在自体造血干细胞移植后，IL-2通常不会出现高水平。因此，我们研究了这些STAT-5信号细胞因子在自体造血干细胞移植后残余Treg细胞扩增中的作用。目前的研究发现，残留的Treg细胞包括存活的外周宿主Foxp3+ CD4+ T细胞，其扩增严重依赖于IL-2，而IL-2仅由存活的宿主细胞提供。然而，IL-7被发现有助于Treg细胞的稳态，但不是作为生长因子，而是作为它们的持久性。结合这种扩展，TCR谱型分析显示，残余宿主Treg细胞区室不同于表现出有限TCR多样性的非条件健康小鼠。总的来说，这些数据表明，造血干细胞移植后Treg和T效应（Teff）细胞的增殖利用了不同的细胞因子池，这对于开发临床策略以在移植后患者中引发所需的免疫反应具有重要意义。
We previously identified a population of residual Treg cells following autologous hematopoietic stem transplantation (HSCT) which rapidly undergoes significant expansion in lymphopenic transplant recipients prior to repopulation by donor de novo derived Treg cells. These CD4+Foxp3+ T cells provide protection from the development of autoimmune disease. Although ablative conditioning results in excess IL-7 and IL-15, IL-2 is typically not found at high levels following autologous HSCT. We therefore examined the role of these STAT-5 signaling cytokines in the expansion of residual Treg cells after autologous HSCT. The present studies found that residual Treg cells include surviving peripheral host Foxp3+ CD4+ T cells whose expansion was critically dependent on IL-2 which could be solely provided by surviving host cells. IL-7 was found to contribute to Treg cell homeostasis, however, not as a growth factor but rather in their persistence. In conjunction with this expansion, TCR spectratype analyses revealed that the residual host Treg cell compartment differed from that present in non-conditioned healthy mice exhibiting a limited TCR diversity. Collectively, these data indicate that the proliferation of Treg and T effector (Teff) cells post-HSCT utilize separate pools of cytokines which has important implications regarding development of clinical strategies to elicit desired immune responses in patients post-transplant.
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通过淋巴结消除来清除稳态细胞因子下沉，增强了采用转移的肿瘤特异性CD8+ T细胞的功效。
影响因子：
15.3
作者：
Gattinoni, Luca;Finkelstein, Steven E;Klebanoff, Christopher A;Antony, Paul A;Palmer, Douglas C;Spiess, Paul J;Hwang, Leroy N;Yu, Zhiya;Wrzesinski, Claudia;Heimann, David M;Surh, Charles D;Rosenberg, Steven A;Restifo, Nicholas P
通讯作者：
Restifo, Nicholas P
影响因子：
4.4
作者：
Burchill, Matthew A.;Yang, Jianying;Farrar, Michael A.
通讯作者：
Farrar, Michael A.
DOI：
10.4049/jimmunol.181.1.225
发表时间：
2008-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bayer AL;Lee JY;de la Barrera A;Surh CD;Malek TR
通讯作者：
Malek TR
影响因子：
20.3
作者：
Bayer, Allison L.;Jones, Monica;Levy, Robert B.
通讯作者：
Levy, Robert B.
影响因子：
4.4
作者：
Granucci, F;Feau, S;Ricciardi-Castagnoli, P
通讯作者：
Ricciardi-Castagnoli, P