| First Author | Salazar-Onfray F | Year | 1997 |
| Journal | J Immunol | Volume | 159 |
| Issue | 7 | Pages | 3195-202 |
| PubMed ID | 9317117 | Mgi Jnum | J:43092 |
| Mgi Id | MGI:1097060 | Doi | 10.4049/jimmunol.159.7.3195 |
| Citation | Salazar-Onfray F, et al. (1997) Down-regulation of the expression and function of the transporter associated with antigen processing in murine tumor cell lines expressing IL-10. J Immunol 159(7):3195-202 |
| abstractText | The MHC class I molecules present antigenic peptides to CTL. The peptides are delivered to the secretory pathway by TAP, which is formed by the association of MHC-encoded TAP1 and TAP2 gene products. Tumor cells incubated or transfected with IL-10 had decreased but peptide-inducible expression of MHC class I, decreased sensitivity to MHC class I-restricted CTL, and increased NK sensitivity. We here demonstrate that IL-10 expression in the murine lymphoma RMA inhibits the TAP-dependent translocation of peptides to the endoplasmic reticulum, resulting in accumulation of immature MHC class I molecules in the endoplasmic reticulum and subsequently low expression of cell surface MHC class I molecules. This finding is explained by a down-regulation of expression of TAP1 and TAP2, observed in IL-10-transfected RMA cells as well as in IL-10-transfected P815 mastocytoma cells. In the J558L plasmacytoma cell line, constitutively expressing high levels of IL-10, increased TAP-dependent translocation of peptides and expression of cell surface MHC class I could be induced by IL-10 antisense expression. IL-10 is the first example to demonstrate that a cytokine can decrease the expression and function of the TAP1/2 molecular complex and, in more general terms, the first example of a cytokine with an inhibitory effect on MHC class I-mediated Ag presentation. |
