التفاصيل البيبلوغرافية
| العنوان: |
HTLV-1 induces a Th1-like state in CD4+CCR4+ T cells. |
| المؤلفون: |
Natsumi Araya1, Tomoo Sato1, Hitoshi Ando1, Utano Tomaru2, Mari Yoshida3, Coler-Reilly, Ariella1, Naoko Yagishita1, Junji Yamauchi1, Atsuhiko Hasegawa4, Mari Kannagi4, Yasuhiro Hasegawa5, Katsunori Takahashi1, Yasuo Kunitomo1, Yuetsu Tanaka6, Toshihiro Nakajima7,8, Kusuki Nishioka7, Atae Utsunomiya9, Jacobson, Steven10, Yoshihisa Yamano1 yyamano@marianna-u.ac.jp |
| المصدر: |
Journal of Clinical Investigation. Aug2014, Vol. 124 Issue 8, p3431-3442. 12p. 1 Color Photograph, 4 Graphs. |
| مصطلحات موضوعية: |
*HTLV-I, *CD4 antigen, *T cells, *TH1 cells, *VIRAL proteins, *SPINAL cord |
| مستخلص: |
Human T-lymphotropic virus type 1 (HTLV-1) is linked to multiple diseases, including the neuroinflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T cell leukemia/lymphoma. Evidence suggests that HTLV-1, via the viral protein Tax, exploits CD4+ T cell plasticity and induces transcriptional changes in infected T cells that cause suppressive CD4+CD25+CCR4+ Tregs to lose expression of the transcription factor FOXP3 and produce IFN-γ, thus promoting inflammation. We hypothesized that transformation of HTLV-1-infected CCR4+ T cells into Th1-like cells plays a key role in the pathogenesis of HAM/TSP. Here, using patient cells and cell lines, we demonstrated that Tax, in cooperation with specificity protein 1 (Sp1), boosts expression of the Th1 master regulator T box transcription factor (T-bet) and consequently promotes production of IFN-γ. Evaluation of CSF and spinal cord lesions of HAM/TSP patients revealed the presence of abundant CD4+CCR4+ T cells that coexpressed the Th1 marker CXCR3 and produced T-bet and IFN-γ. Finally, treatment of isolated PBMCs and CNS cells from HAM/TSP patients with an antibody that targets CCR4+ T cells and induces cytotoxicity in these cells reduced both viral load and IFN-γ production, which suggests that targeting CCR4+ T cells may be a viable treatment option for HAM/TSP. [ABSTRACT FROM AUTHOR] |
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