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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.

ABSTRACT: 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-ßRII) 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-? 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-?-mediated Treg cell suppression of IL-2 transcription is modulated through alterations in NFAT2 binding to the IL-2 promoter.

SUBMITTER: Meng L

PROVIDER: S-EPMC3887409 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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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.

Meng Liping L Tompkins Mary M Miller Michelle M Fogle Jonathan J

AIDS research and human retroviruses 20130830 1

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-ßRII) 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 ...[more]

PMID: 23924068

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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.

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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.

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