| First Author | Zhang E | Year | 2019 |
| Journal | J Immunol | Volume | 203 |
| Issue | 11 | Pages | 2872-2886 |
| PubMed ID | 31636238 | Mgi Jnum | J:282141 |
| Mgi Id | MGI:6379981 | Doi | 10.4049/jimmunol.1900065 |
| Citation | Zhang E, et al. (2019) TLR2 Stimulation Increases Cellular Metabolism in CD8(+) T Cells and Thereby Enhances CD8(+) T Cell Activation, Function, and Antiviral Activity. J Immunol 203(11):2872-2886 |
| abstractText | TLR2 serves as a costimulatory molecule on activated T cells. However, it is unknown how the functionality and antiviral activity of CD8(+) T cells are modulated by direct TLR2 signaling. In this study, we looked at the TLR2-mediated enhancement of TCR-driven CD8(+) T cell activation in vitro and in woodchuck hepatitis virus transgenic mice. In vitro stimulation of CD8(+) T cells purified from C57BL/6 mice showed that TLR2 agonist Pam3CSK4 directly enhanced the TCR-dependent CD8(+) T cell activation. Transcriptome analysis revealed that TLR2 signaling increased expression of bioenergy metabolism-related genes in CD8(+) T cells, such as IRF4, leading to improved glycolysis and glutaminolysis. This was associated with the upregulation of genes related to immune regulation and functions such as T-bet and IFN-gamma. Glycolysis and glutaminolysis were in turn essential for the TLR2-mediated enhancement of T cell activation. Administration of TLR2 agonist Pam3CSK4 promoted the expansion and functionality of vaccine-primed, Ag-specific CD8(+) T cells in both wild type and transgenic mice and improved viral suppression. Thus, TLR2 could promote CD8(+) T cell immunity through regulating the energy metabolism. |
