| First Author | Bucks CM | Year | 2009 |
| Journal | J Immunol | Volume | 182 |
| Issue | 11 | Pages | 6697-708 |
| PubMed ID | 19454664 | Mgi Jnum | J:148871 |
| Mgi Id | MGI:3847038 | Doi | 10.4049/jimmunol.0800997 |
| Citation | Bucks CM, et al. (2009) Chronic antigen stimulation alone is sufficient to drive CD8+ T cell exhaustion. J Immunol 182(11):6697-708 |
| abstractText | The failure of CD8(+) T cells to respond to chronic infection has been termed 'exhaustion' and describes the condition in which CD8(+) T cells exhibit reduced differentiation, proliferation, and effector function. CD8(+) T cell exhaustion has been extensively studied in the murine model of chronic infection, lymphocytic choriomeningitis virus (LCMV). Although LCMV-based studies have yielded many interesting findings, they have not allowed for discrimination between the roles of cytokine- and Ag-driven exhaustion. We have created a system of chronic Ag stimulation using murine influenza A virus that leads to exhaustion and functional disability of virus-specific CD8(+) T cells, in the absence of high viral titers, sustained proinflammatory cytokine production and lymphocyte infection. Our findings show that Ag alone is sufficient to drive CD8(+) T cell impairment, that Ag-driven loss of virus-specific CD8(+) T cells is TRAIL mediated, and that removal of Ag reverses exhaustion. Although programmed death 1 was up-regulated on chronic Ag-stimulated CD8(+) T cells, it played no role in the exhaustion. These findings provide a novel insight into the mechanisms that control functional exhaustion of CD8(+) T cells in chronic infection. |
