کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2832293 1163834 2007 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Differential modulation of mitogen driven proliferation and homeostasis driven proliferation of T cells by rapamycin, Ly294002 and chlorophyllin
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Differential modulation of mitogen driven proliferation and homeostasis driven proliferation of T cells by rapamycin, Ly294002 and chlorophyllin
چکیده انگلیسی

Homeostasis driven proliferation (HDP) of naïve CD4+ T cells depends upon T cell receptor ligation with self-MHC II along with availability of interleukin-7. But the exact nature of downstream signaling events involved in HDP of helper T cells remains elusive. To identify the specific involvement of signaling molecules in HDP, purified CD4+ T cells were treated with either mTOR inhibitor rapamycin or PI3kinase inhibitor Ly294002 or with an antioxidant chlorophyllin (CHL) in vitro. Rapamycin treated cells failed to proliferate, expressed anergic T cell specific transcription factor genes egr-2 and egr-3 and showed diminished IFN-γ production in response to Con A stimulation in vitro. Although CHL treated cells also failed to proliferate, they showed a normal IFN-γ production during primary stimulation and did not upregulate egr-2 and egr-3 genes following restimulation in vitro. Ly294002 treated cells failed to express IL-2 and IFN-γ and did not divide in response to Con A stimulation in vitro. While all these inhibitors significantly inhibited CD4+ T cell proliferation in response to the mitogen in vitro, only CHL treatment could inhibit their HDP in lymphopenic mice. Our results also demonstrate that combined treatment with rapamycin and Ly294002 did not inhibit HDP of CD4+ T cells. Thus, the present study, for the first time, shows a non-essential role of mTOR and PI3kinase during HDP of CD4+ T cells and also describes its possible regulation by an antioxidant.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 44, Issue 11, April 2007, Pages 2831–2840
نویسندگان
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