Lentivirus-Activated T Regulatory Cells Suppress T Helper Cell Interleukin-2 Production by Inhibiting Nuclear Factor of Activated T Cells 2 Binding to the Interleukin-2 Promoter

被引:0
作者
Meng, Liping [1 ]
Tompkins, Mary [1 ]
Miller, Michelle [1 ]
Fogle, Jonathan [1 ]
机构
[1] N Carolina State Univ, Coll Vet Med, Dept Populat Hlth & Pathobiol, Program Immunol, Raleigh, NC 27607 USA
关键词
FIV INFECTION; NFAT; EXPRESSION; MECHANISM; GENE; AUTOREGULATION; APOPTOSIS; CATS;
D O I
10.1089/aid.2013.0062
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Using the feline immunodeficiency virus (FIV) model for AIDS lentivirus infection, we previously demonstrated that Treg cells from FIV-infected cats up-regulate membrane-associated tumor growth factor beta (mTGF-ss) during the course of infection and that activated T lymphocytes up-regulate TGF-ss receptor II (TGF-ss RII) during the course of infection. Furthermore, we have demonstrated that autologous coculture of Tregs with Th cells from FIV-infected cats leads to suppression of interleukin (IL)-2 production and loss of proliferation in a TGF-ss-dependent fashion. Nuclear factor of activated T cells (NFAT) 2 has been identified as integral to effector Th cell maturation and function by promoting IL-2 transcription. Therefore, we questioned whether NFAT2 expression might be altered by TGF- signaling. Feline NFAT2 exon sequences were identified based upon sequence homology to human and murine NFAT2. Following stimulation, IL-2 and NFAT2 mRNA levels were similarly increased in both FIV- and FIV+ cats. Activated CD4(+)CD25(-) cells from both FIV- and FIV+ cats cocultured with autologous CD4(+)CD25(+) cells or treated with TGF-beta demonstrated decreased IL-2 production; however, NFAT2 mRNA levels were unaffected. Although NFAT2 mRNA levels were unaffected, chromatin immunoprecipitation (ChIP) for NFAT2 indicated decreased NFAT2 binding at the IL-2 promoter in suppressed Th cells. These data suggest that TGF-beta-mediated Treg cell suppression of IL-2 transcription is modulated through alterations in NFAT2 binding to the IL-2 promoter.
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页码:58 / 66
页数:9
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