| First Author | Ngoi SM | Year | 2012 |
| Journal | Proc Natl Acad Sci U S A | Volume | 109 |
| Issue | 26 | Pages | 10486-91 |
| PubMed ID | 22689946 | Mgi Jnum | J:185595 |
| Mgi Id | MGI:5429463 | Doi | 10.1073/pnas.1202607109 |
| Citation | Ngoi SM, et al. (2012) Presensitizing with a Toll-like receptor 3 ligand impairs CD8 T-cell effector differentiation and IL-33 responsiveness. Proc Natl Acad Sci U S A 109(26):10486-91 |
| abstractText | The synthetic double-stranded RNA poly(I:C) is commonly used as an adjuvant to boost CD8 T-cell function; however, polyinosinic:polycytidylic acid [poly(I:C)] can also suppress autoimmune disease. The mechanism by which a single adjuvant achieves two distinct immunoregulatory roles is unknown. Although it is clear that coadministration of poly(I:C) with antigen elicits strong adjuvant effects in mice, we found that poly(I:C) injection before antigen substantially reduced antigen-dependent CD8 T-cell responses. Notably, CD8 T cells sensitized in poly(I:C)-pretreated mice failed to fully up-regulate IL-33R (ST2), which led to impaired T-cell receptor-independent responses to IL-33. In contrast, nonsensitized effector CD8 T cells responded robustly to IL-33 using a two-signal cytokine mechanism. During an acute lung response to Staphylococcus aureus enterotoxin, peripheral injection of poly(I:C) manifested a suppressive process by inhibiting the differentiation of both antigen- and IL-33-responsive CD8 effectors systemically. These findings highlight that early exposure to double-stranded RNA reverses its role as an adjuvant and, importantly, prevents IL-33R up-regulation on CD8 effector T cells to dampen inflammation. |
