Dominant expression of interleukin-10 and transforming growth factor-beta 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 IFN gamma, IL-10, transforming growth factor-beta (TGF beta), and cytotoxic T lymphocyte antigen-4 (CTLA4) mRNA than HLA-DR(-)T-cells. HLA-DR(+) T cells of IM patients transcribed more IFN gamma and IL-10 than their HLA-DR(-)T cells. Expression levels of IFN gamma 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, IFN gamma, CTLA4, TGF beta, 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 TGF beta. These results suggest that CAEBV T-cells are activated to transcribe IFN gamma, IL-10, and TGF beta 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.
Ohga
Shouichi
S
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. ohgas@pediatr.med.kyushu-u.ac.jp
Nomura
Akihiko
A
Takada
Hidetoshi
H
Tanaka
Tamami
T
Furuno
Kenji
K
Takahata
Yasushi
Y
Kinukawa
Naoko
N
Fukushima
Noriyasu
N
Imai
Shosuke
S
Hara
Toshiro
T
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D020031:Epstein-Barr Virus Infections / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D005260:Female; D015870:Gene Expression; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics*; D008213:Lymphocyte Activation; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000235:genetics*
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma