| First Author | Nansen A | Year | 2002 |
| Journal | Blood | Volume | 99 |
| Issue | 4 | Pages | 1237-45 |
| PubMed ID | 11830471 | Mgi Jnum | J:74713 |
| Mgi Id | MGI:2158997 | Doi | 10.1182/blood.v99.4.1237 |
| Citation | Nansen A, et al. (2002) The role of CC chemokine receptor 5 in antiviral immunity. Blood 99(4):1237-45 |
| abstractText | The CC chemokine receptor CCR5 is an important coreceptor for human immunodeficiency virus (HIV), and there is a major thrust to develop anti-CCR5-based therapies for HIV-1. However, it is not known whether CCR5 is critical for a normal antiviral T-cell response. This study investigated the immune response to lymphocytic choriomeningitis virus in mice lacking CCR5 (CCR5(-/-) mice). This infection is a classical model for studying antiviral immunity, and influx of CCR5-expressing CD8(+) T cells and macrophages is essential for both virus control and associated immunopathology. Results showed that the virus-induced clonal expansion of antigen-specific T cells was augmented in CCR5(-/-) mice especially with regard to the CD4(+) subset. Despite absence of CCR5, intracerebral infection invariably resulted in lethal T cell-mediated meningitis, and quantitative and qualitative analysis of the inflammatory exudate cells did not reveal any significant differences between gene-targeted mice and wild-type controls. CCR5 was also found to be redundant regarding the ability to eliminate virus from internal organs. Using delayed-type hypersensitivity to evaluate CD8(+) T cell-mediated inflammation, no significant influence of CCR5 was found, not even when viral peptide was used as local trigger instead of live virus. Finally, long-term CD8(+) T cell-mediated immune surveillance was efficiently sustained in CCR5(-/-) mice. Taken together, these results indicate that expression of CCR5 is not critical for T cell-mediated antiviral immunity, and this molecule may therefore constitute a logic and safe target for anti-HIV therapies. (Blood. 2002;99:1237-1245) |
