Dominant expression of interleukin-10 and transforming growth factor-β genes in activated T-cells of chronic active Epstein-Barr virus infection

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.