Abstract
We have reported that in vivo administration of the toll-like receptor 3 ligand (TLRL) poly (I:C) induced rapid stimulation of the innate mediators, including NK cells, Mϕ, dendritic cells, and inflammatory cytokines. These effects strikingly augmented post vaccination CD8 T cells responses. It is not clear, however, whether poly (I:C) acts directly on CD8 T cells. Therefore, we analyzed the expression of TLRs on both CD4 and CD8 T cells and tested whether CD8 T cells respond directly to poly (I:C). Real-time PCR analysis revealed that TLRs (TLR1-TLR13) are expressed in the purified CD4 and CD8 T cells, and their in vitro treatment with 50 μg/ml poly 10 nM PMA, or with OVA peptide-pulsed splenocytes modulated the expression of the tested TLRs. Utilizing OT-1 TCR adoptive transfer transgenic mouse model, in vitro treatment of purified naïve OT-1 cells with 50 μg/ml poly (I:C) for 18 hours in the absence of antigen stimulation triggered their activation as evidenced by upregulation of the early activation markers CD69 and CD25, and downregulation of CD62L expression. Importantly, when these cells were adoptively transferred into naïve recipient followed by peptide vaccination, they showed superior expansion and activation to their naïve counterparts. These results clearly reveal a direct effect of poly (I:C) on CD8 T cells and supports the notion of direct involvement of TLRs in adaptive immune responses.
