| First Author | Ngoi SM | Year | 2008 |
| Journal | J Immunol | Volume | 181 |
| Issue | 11 | Pages | 7670-80 |
| PubMed ID | 19017955 | Mgi Jnum | J:142198 |
| Mgi Id | MGI:3820723 | Doi | 10.4049/jimmunol.181.11.7670 |
| Citation | Ngoi SM, et al. (2008) Targeting poly(I:C) to the TLR3-independent pathway boosts effector CD8 T cell differentiation through IFN-alpha/beta. J Immunol 181(11):7670-80 |
| abstractText | Poly(I:C) is an adjuvant used for antitumor treatment and vaccines because of its prominent effects on CD8 T cells and NK cells. Poly(I:C) binds TLR3 and this interaction is thought to be central for driving cell-mediated immune responses. We investigated the importance of TLR3 in poly(I:C)-mediated endogenous CD8 T cell responses using the pathogenic T cell stimulant Staphylococcus aureus enterotoxin A. While the responsive CD8 T cells expanded comparably in both wild-type and TLR3(-/-) mice, differentiation of effector CD8 T cells was enhanced by poly(I:C) in the TLR3(-/-) mice. A higher percentage of Ag-specific CD8 T cells became IFN-gamma and TNF-alpha producers in the absence of TLR3 signaling. Consistent with this boosted response was the observation that TLR3-deficient cells synthesized less IL-10 compared with TLR3-sufficient cells in response to poly(I:C). Ultimately, however, the fundamental mechanism of CD8 effector T cell differentiation through the TLR3-independent pathway was shown to be completely IFN-alpha/beta-dependent. Administration of IFN-alpha/beta-neutralizing Abs abolished the poly(I:C) effects in TLR3(-/-) mice. These findings reveal specific roles of how dsRNA receptors shape CD8 T cell responses, which should be considered as poly(I:C) is authenticated as a therapeutic adjuvant used in vaccines. |
