Dominant expression of interleukin-10 and transforming growth factor-β genes in activated T-cells of chronic active epstein–barr virus infection
✍ Scribed by Shouichi Ohga; Akihiko Nomura; Hidetoshi Takada; Tamami Tanaka; Kenji Furuno; Yasushi Takahata; Naoko Kinukawa; Noriyasu Fukushima; Shosuke Imai; Toshiro Hara
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 201 KB
- Volume
- 74
- Category
- Article
- ISSN
- 0146-6615
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✦ Synopsis
Abstract
Chronic active Epstein–Barr virus (EBV) infection is a chronic mononucleosis syndrome associated with clonal proliferation of EBV‐carrying T‐/natural killer (NK)‐cells. High levels of circulating EBV and activated T‐cells are sustained during the prolonged disease course, whereas it is not clear how ectopic EBV infection in T‐/NK‐cells has been established and maintained. To assess the biological role of activated T‐cells in chronic active EBV infection (CAEBV), EBV DNA and cellular gene expressions in peripheral T‐cells were quantified in CAEBV and infectious mononucleosis (IM) patients. In CAEBV, HLA‐DR^+^ T‐cells had higher viral load and larger amounts of IFNγ, IL‐10, transforming growth factor‐beta (TGFβ), and cytotoxic T lymphocyte antigen‐4 (CTLA4) mRNA than HLA‐DR^−^T‐cells. HLA‐DR^+^ T cells of IM patients transcribed more IFNγ and IL‐10 than their HLA‐DR^−^T cells. Expression levels of IFNγ and forkhead box p3 (Foxp3) in CAEBV HLA‐DR^+^ T‐cells were higher than in IM HLA‐DR^+^ T‐cells. The effective variables to discriminate the positivity of HLA‐DR were IL‐10, IFNγ, CTLA4, TGFβ, and IL‐2 in the order of statistical weight. EBV load in CAEBV T‐cells correlated with the expression levels of only IL‐10 and TGFβ. These results suggest that CAEBV T‐cells are activated to transcribe IFNγ, IL‐10, and TGFβ excessively, and the latter two genes are expressed preferentially in the EBV‐infected subsets. The dominant expression of regulatory cytokines in T‐cells may imply a viral evasion mechanism in the disease. J. Med. Virol. 74:449–458, 2004. © 2004 Wiley‐Liss, Inc.