| First Author | Raué HP | Year | 2004 |
| Journal | J Immunol | Volume | 173 |
| Issue | 11 | Pages | 6873-81 |
| PubMed ID | 15557182 | Mgi Jnum | J:94360 |
| Mgi Id | MGI:3512642 | Doi | 10.4049/jimmunol.173.11.6873 |
| Citation | Raue HP, et al. (2004) Activation of virus-specific CD8+ T cells by lipopolysaccharide-induced IL-12 and IL-18. J Immunol 173(11):6873-81 |
| abstractText | Virus-specific T cells represent a hallmark of Ag-specific, adaptive immunity. However, some T cells also demonstrate innate functions, including non-Ag-specific IFN-gamma production in response to microbial products such as LPS or exposure to IL-12 and/or IL-18. In these studies we examined LPS-induced cytokine responses of CD8(+) T cells directly ex vivo. Following acute viral infection, 70-80% of virus-specific T cells will produce IFN-gamma after exposure to LPS-induced cytokines, and neutralization experiments indicate that this is mediated almost entirely through production of IL-12 and IL-18. Different combinations of these cytokines revealed that IL-12 decreases the threshold of T cell activation by IL-18, presenting a new perspective on IL-12/IL-18 synergy. Moreover, memory T cells demonstrate high IL-18R expression and respond effectively to the combination of IL-12 and IL-18, but cannot respond to IL-18 alone, even at high cytokine concentrations. This demonstrates that the synergy between IL-12 and IL-18 in triggering IFN-gamma production by memory T cells is not simply due to up-regulation of the surface receptor for IL-18, as shown previously with naive T cells. Together, these studies indicate how virus-specific T cells are able to bridge the gap between innate and adaptive immunity during unrelated microbial infections, while attempting to protect the host from cytokine-induced immunopathology and endotoxic shock. |
