دورية أكاديمية

HTLV-1 bZIP factor impairs cell-mediated immunity by suppressing production of Th1 cytokines.

التفاصيل البيبلوغرافية
العنوان: HTLV-1 bZIP factor impairs cell-mediated immunity by suppressing production of Th1 cytokines.
المؤلفون: Sugata, Kenji1, Satou, Yorifumi1, Yasunaga, Jun-ichirou1, Hara, Hideki2, Ohshima, Kouichi3, Utsunomiya, Atae4, Mitsuyama, Masao2, Matsuoka, Masao1 mmatsuok@virus.kyoto-u.ac.jp
المصدر: Blood. 1/12/2012, Vol. 119 Issue 2, p434-444. 11p.
مصطلحات موضوعية: *CELLULAR immunity, *LEUKEMIA, *IMMUNODEFICIENCY, *TRANSGENIC mice, *LISTERIA monocytogenes, *LEUCINE zippers
مستخلص: Adult T-cell leukemia (ATL) patients and human T-cell leukemia virus-1 (HTLV-1) infected individuals succumb to opportunistic infections. Cell mediated immunity is impaired, yet the mechanism of this impairment has remained elusive. The HTLV-1 basic leucine zipper factor (HBZ) gene is encoded in the minus strand of the viral DNA and is constitutively expressed in infected cells and ATL cells. To test the hypothesis that HBZ contributes to HTLV-1 associated immunodeficiency, we challenged transgenic mice that express the HBZ gene in CD4 T cells (HBZ-Tg mice) with herpes simplex virus type 2 or Listeria monocytogenes, and evaluated cellular immunity to these pathogens. HBZ-Tg mice were more vulnerable to both infections than non-Tg mice. The acquired immune response phase was specifically suppressed, indicating that cellular immunity was impaired in HBZ-Tg mice. In particular, production of interferon-γ (IFN-γ) by CD4 T cells was suppressed in HBZ-Tg mice. HBZ suppressed transcription from the IFN-γ gene promoter in a CD4 T-cell intrinsic manner by inhibiting nuclear factor of activated T cells and the activator protein 1 signaling pathway. This study shows that HBZ inhibits CD4 T-cell responses by directly interfering with the host cell-signaling pathway, resulting in impaired cell-mediated immunity in vivo. [ABSTRACT FROM AUTHOR]
قاعدة البيانات: Academic Search Index
الوصف
تدمد:00064971
DOI:10.1182/blood-2011-05-357459