Abstract
BACKGROUND: It is difficult to experimentally infect volunteers with RV strains to which the subject demonstrates serological immunity. However, in RV challenges, viral clearance begins before de novo adaptive immune responses would develop. We speculated that adaptive immunity to RV reflects heterologous immunity by effector memory cells. METHODS: DCs were generated from monocytes using GM-CSF and IL-4 and RV39 loading accomplished with a dose of ∼ 350 TCID50/10(5) cells. RV-induced maturation was established as modulation of MHC class II, CD80, CD83, and CD86. Circulating RV targeting CD4 and CD8 T cells were investigated as induction of RV-specific proliferation (CFSE-dilution). RESULTS: Maturation of DC by RV was confirmed as upregulation of MHC Class II (83.3 ± 5.0% to 87.8 ± 4.1%), CD80 (39.4 ± 7.2% to 47.6 ± 7.7%) and CD86 (78.4 ± 4.7% to 84.1 ± 3.4%). Both CD4 and CD8 memory T cells were recognized in the circulation of healthy subjects. CONCLUSIONS: RV drives DC maturation and results in their ability to present RV antigens to both T helper and cytotoxic lymphocytes. Both CD4 and CD8 cells capable of recognizing RV-associated antigens are present in the circulation of healthy subjects where they are presumably involved in immune surveillance and explain the rapid recruitment of an adaptive immune response during RV infection.