CCR5 is required for regulation of alloreactive T-cell responses to single class II MHC-mismatched murine cardiac grafts.
CCR5 is required for regulation of alloreactive T-cell responses to single class II MHC-mismatched murine cardiac grafts.
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DOI：
10.1111/j.1600-6143.2009.02786.x
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发表时间：
2009-10
期刊：
影响因子：
--
通讯作者：
Fairchild RL
中科院分区：
文献类型：
--
作者：
Nozaki T;Rosenblum JM;Schenk AD;Ishii D;Fairchild RL
在单一的II类MHC不同的B6.H-2bm12心脏移植物中，野生型C57BL/6受者的效应性CD4T细胞反应受到CD4+CD25+调节性T细胞(Treg)的限制，从而导致移植物的长期存活。为了研究趋化因子受体在Treg功能中可能发挥的作用，本研究测试了B6.H-2bm12心脏移植后C57BL/6受体对Tregs上CCR5抑制同种免疫反应的需求。与B6.H-2bm12同种异体移植物在野生型受体中的长期存活(>；100天)相反，在CD4T细胞大量渗透的CCR5/-受体中，同种异体移植物在25天内被急性排斥。与野生型受体相比，B6CCR5-/-受者脾中产生干扰素-γ和IL-4的供者反应性CD4T细胞的数量和持续时间显著增加。野生型和B6型CCR5-/-小鼠移植前后脾FoxP3+Tregs的数量相同，且这些Tregs在体外具有相同的抑制作用。但在B6.CCR5-/-受体中，FoxP3+Treg细胞在B6.H-2bm12同种异体移植物中的数量减少。向CCR5-/-受体过继转移野生型但不是CCR5缺陷的CD4+CD25+Tregs恢复了B6.H-2bm12心脏移植物的长期存活。总之，这些结果表明，CCR5的表达是Tregs调节功能所必需的，该功能限制了单个II类MHC不匹配的同种异体心脏移植物的同种反应性CD4T细胞的反应。
The effector CD4 T cell response in wild-type C57BL/6 recipients of single class II MHC-disparate B6.H-2bm12 cardiac allografts is restricted by CD4+CD25+ regulatory T cells (Tregs) resulting in long-term allograft survival. To investigate the role chemokine receptors might play in Treg function, this study tested the requirement for CCR5 on Tregs to suppress the alloimmune response in C57BL/6 recipients of B6.H-2bm12 cardiac allografts. In contrast to the long-term survival of B6.H-2bm12 allografts in wild-type recipients (>100 days), the allografts were acutely rejected within 25 days in CCR5-/- recipients with intense infiltration of CD4 T cells. Numbers and duration of donor-reactive CD4 T cells producing IFN-γ and IL-4 were markedly increased in spleens of B6.CCR5-/- vs. wild-type recipients. Wild-type and B6.CCR5-/- mice had equivalent numbers of splenic FoxP3+ Tregs before and following transplantation, and these Tregs were equivalently suppressive in vitro. However, diminished numbers of FoxP3+ Tregs infiltrated B6.H-2bm12 allografts in B6.CCR5-/- recipients. Adoptive transfer of wild-type, but not CCR5-deficient, CD4+CD25+ Tregs to CCR5-/- recipients restored long-term survival of B6.H-2bm12 cardiac grafts. Collectively, these results indicate that CCR5 expression is required for the regulatory functions of Tregs that restrict alloreactive CD4 T cell responses to single class II MHC-mismatched cardiac allografts.
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介导同种异体移植耐受性的FOXP3+ T调节细胞的募集取决于CCR4趋化因子受体。
影响因子：
15.3
作者：
Lee, I;Wang, LQ;Wells, AD;Dorf, ME;Ozkaynak, E;Hancock, WW
通讯作者：
Hancock, WW
DOI：
10.1084/jem.160.4.1184
发表时间：
1984-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Mengle-Gaw L;Conner S;McDevitt HO;Fathman CG
通讯作者：
Fathman CG
影响因子：
4.4
作者：
Moreira, Ana Paula;Cavassani, Karen Angelica;Silva, Joao S.
通讯作者：
Silva, Joao S.
影响因子：
8.8
作者：
Bickerstaffa, A.;Nozaki, T.;Fairchild, R. L.
通讯作者：
Fairchild, R. L.
影响因子：
4.4
作者：
Schenk, S;Kish, DD;Fairchild, RL
通讯作者：
Fairchild, RL