The TLR3 agonist poly(I:C) targets CD8+ T cells and augments their antigen-specific responses upon their adoptive transfer into naïve recipient mice.
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.
Salem
Mohamed L
ML
Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA; Department of Zoology, Faculty of Science, Tanta University, Tanta, Egypt.
Diaz-Montero
C Marcela
CM
El-Naggar
Sabry A
SA
Chen
Yian
Y
Moussa
Omar
O
Cole
David J
DJ
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011070:Poly I-C / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D051196:Toll-Like Receptor 3 / Q000819:agonists* / Q000276:immunology / Q000378:metabolism; D014611:Vaccination
D051196:Toll-Like Receptor 3; D011070:Poly I-C