The TLR3 agonist PolyI:C targets CD8(+) T-cells and augments their antigen-specific responses upon their adoptive transfer into naïve recipient mice

Department of Zoology, Faculty of Science, Tanta University, Tanta, Egypt
Vaccine (Impact Factor: 3.62). 01/2009; 27(4):549-557. DOI: 10.1016/j.vaccine.2008.11.013


We have recently reported that the toll-like receptor 3 (TLR3) agonist poly(I:C) induces adjuvant effects to post vaccination CD8+ T cells responses through rapid induction of innate mediators, including NK cells, macrophages, dendritic cells (DCs), and inflammatory cytokines. However, whether this TLR3 agonist directly targets CD8+ T cells needs to be carefully investigated. In this study, we found that optimal post vaccination CD8+ T cell responses to ex vivo DC-based vaccination requires triggering of TLR3 signaling pathway in DCs in vitro as well as in the recipient host, indicating a role for other cell types. Real-time PCR analysis revealed that TLRs (TLR1–TLR13) are expressed in purified (>99% pure) CD4+ and CD8+ T cells from C57BL/6 and BALB/c mice, where the magnitude of the expression was strain and cell type dependent. In vitro, treatment of these purified T cells with poly(I:C) modulated the expression of TLRs including TLR3. Furthermore, non-specific and antigen-specific stimulation of CD8+ T cells by phorbol myristate acetate and MHC class I peptide-pulsed splenocytes, respectively, modulated TLR expression in purified CD4+ and CD8+ T cells. Importantly, brief conditioning of purified naïve TCR transgenic OT-1 (CD8+) T cells in vitro with poly(I:C) induced activation of these cells in absence of antigen stimulation. Interestingly, when these in vitro poly(I:C)-conditioned OT-1 cells were adoptively transferred into naïve recipient followed by peptide vaccination, they showed superior expansion and activation to their naïve counterparts. These results suggest that CD8+ T cells can be activated by triggering their TLR3. Furthermore, the data support the notion of direct involvement of TLRs in adaptive immune responses.

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Available from: Mohamed Labib Salem, Dec 08, 2014
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    • "On SSC15, a QTL for CD4:CD8 ratio was mapped to the region proximal to the TLR3 (toll-like receptor 3) gene. Salem et al. [52] suggested that CD8+ T cells can be activated by triggering their TLR3. The ADA (adenosine deaminase) gene is located close to the QTL for proportion of CD4+CD8+ on SSC17. "
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    • "Virally infected T cell lines [34], as well as CD8 + T cells and B cells [40] from virally infected individuals also showed altered TLR expression levels. We have also found that the adjuvant effects of poly(I:C) on OT-1 (CD8 + ) T cells during their antigen stimulation in vitro were associated with upregulation of the expression levels of TLR expression in these cells [3], suggesting that CD8 + T cells respond directly to the TLR3L poly(I:C). Taken together, these data suggest that modulation of TLR expression in cells of adaptive immunity upon their activation might be a possible mechanism to regulate the ongoing T cell-mediated immunity. "
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    • "BM-derived DCs were generated as we previously described [55] [56] [57]. Briefly, BM was flushed from the femurs and tibias of mice and then depleted of red blood cells by lysis with ACK buffer (Biofluids, Camarillo, CA). "
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