Impact of Human Mutant TGFβ1/Fc Protein on Memory and Regulatory T Cell Homeostasis Following Lymphodepletion in Nonhuman Primates.
Impact of Human Mutant TGFβ1/Fc Protein on Memory and Regulatory T Cell Homeostasis Following Lymphodepletion in Nonhuman Primates.
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DOI：
10.1111/ajt.13883
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发表时间：
2016-10
期刊：
影响因子：
--
通讯作者：
Ezzelarab MB
中科院分区：
文献类型：
--
作者：
Guo H;Lu L;Wang R;Perez-Gutierrez A;Abdulkerim HS;Zahorchak AF;Sumpter TL;Reimann KA;Thomson AW;Ezzelarab MB
Transforming growth factor β1 (TGFβ1) plays a key role in T cell homeostasis and peripheral tolerance. We evaluated the influence of a novel human mutant TGFβ1/Fc protein on memory CD4+ and CD8+ Tcell (Tmem) responses in vitro and their recovery following anti-thymocyte globulin (ATG)-mediated lymphodepletion in monkeys. TGFβ1/Fc induced Smad-2/3 protein phosphorylation in rhesus and human peripheral blood mononuclear cells and augmented the suppressive effect of rapamycin on rhesus Tmem proliferation after either alloactivation or anti-CD3/CD28 stimulation. In combination with IL-2, the incidence of CD4+CD25hiFoxp3hi regulatory T cells (Treg) and Treg/Th17 ratios were increased. In lymphodepleted monkeys, whole blood trough levels of infused TGFβ1/Fc were maintained between 2–7 μg/mL for 35 days. Following ATG administration, total T cell numbers were reduced markedly. In those given TGFβ1/Fc infusion, CD8+T cell recovery to pre-depletion levels was delayed compared to controls. Additionally, numbers of CD4+CD25hiCD127lo Treg increased at 4–6 weeks after depletion but subsequently declined to pre-depletion levels by 12 weeks. In all monkeys, CD4+CD25hiFoxp3hi Treg/CD4+IL-17+ cell ratios were reduced, particularly after stopping TGFβ1/Fc infusion. Thus, human TGFβ1/Fc infusion may delay Tmem recovery following lymphodepletion in nonhuman primates. Combined (low-dose) IL-2 infusion may be required to improve the Treg/Th17 ratio following lymphodepletion.
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DOI：
10.1111/j.1600-6143.2009.02826.x
发表时间：
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期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
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影响因子：
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发表时间：
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期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
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