Background –Primary infection with human herpes virus 6 (mainly HHV-6B) commonly occurs in the first two years of life leading to persistence and the possibility of virus reactivation later in life. Consequently, a specific cellular immune response is essential for effective control of virus reactivation. We have studied cell-mediated immune response to HHV-6 in healthy children and adolescents.
Materials and Methods -  By flow cytometry, the amount of cytokine (interferon gamma – IFN- γ, interleukin 2 – IL-2, tumour necrosis factor alpha – TNF-α) secreting T-cells after 10 days of pre-sensitization and 6 hours of re-stimulation were measured with mixtures of pooled overlapping peptides from HHV-6 specific protein U54, staphylococcal enterotoxin B (SEB, positive control) or Actin (negative control) in healthy children and adolescents without any underlying immune disorder or infectious disease.

Results - All 25 tested individuals (age 3.1-18.3, median 8.2 years, 28% female) showed a virus-specific response for at least one cytokine in either CD4+ or CD8+ cells. Percentages of individuals with HHV-6-specific TNF-α response in CD4+ (48% of individuals) as well as CD8+ (56% of individuals) were almost the highest. Our data show significantly higher frequencies of HHV-6-specific TNF-α producing CD8+ T-cells in individuals older than 10 years of life (n=12, p=0.033). Additionally, the frequency of TNF-α producing CD8+ T-cells positively correlated with the age of the individuals (Spearman-Rho, r=0.465) on a two-sided significance level of p=0.019. 
Conclusions - HHV-6 specific T-cells are commonly present, expandable, and detectable in healthy children and adolescents with higher frequencies of antigen-specific T-cells in older children and adolescents possibly reflecting repeated stimulation by viral persistence and subclinical reactivation.

SPECIFIC T-CELL IMMUNITY AGAINST HHV-6 IN HEALTHY CHILDREN AND ADOLESCENTS