The CC chemokine receptor CCR5 is not crucial for T-cell-mediated anti-viralimmunity, validating the use of CCR5 as a target for HIV therapies.
The CC chemokine receptor CCR5 is an important co-receptor for HIV, and patients who lack this receptor have a reduced susceptibility to infection. Anti-CCR5-based therapies for HIV are being developed, but the role of CCR5 in normal antiviral responses has not been directly investigated. Nansen and colleagues now report in Blood that CCR5 is not crucial for T-cell-mediated antiviral immunity, validating the use of CCR5 as a target for HIV therapies.
The authors used the murine lymphocytic choriomeningitis virus (LCMV) model to compare the antiviral responses of CCR5-/- and wild-type mice. Infection with LCMV normally induces the generation of activated CD4+ and CD8+ T cells, which are important for clearing the viral infection and which cause inflammation of infected organs. Intracerebral infection leads to fatal T-cell-mediated meningitis. To investigate the importance of CCR5 expression for the generation of LCMV-specific T cells, the frequency of virus-specific CD4+ and CD8+ T cells in the spleens of CCR5-/- and wild-type mice were compared. Virus-induced clonal expansion of antigen-specific T cells, particularly CD4+ cells, was actually enhanced in the CCR5-/- mice.
Do these CCR5-/- LCMV-specific T cells clear the virus effectively? The kinetics of viral clearance in the spleen, liver and lungs was similar in the CCR5-/- and wild-type mice, showing that cytolytic T-cell function in, and homing to, infected organs is not affected in the absence of CCR5. Despite lacking expression of CCR5, the knockouts succumb to lethal T-cell-mediated meningitis following intracerebral infection. In addition, the authors found no significant differences between the knockout and wild-type mice in the recruitment of monocytes/macrophages to the inflamed meninges or in the cerebral chemokine and CCR gene expression. Analysis of the long-term CD8+ T-cell-mediated response to LCMV also showed a redundant role for CCR5 in the memory phase of LCMV infection.
The authors conclude that CCR5 expression is not crucial for T-cell-mediated antiviral immunity and that there are positive prospects for anti-CCR5 HIV therapies.
Jenny Buckland
References
ORIGINAL RESEARCH PAPER Nansen, A. et al. The role of CC chemokine receptor 5 in antiviral immunity. Blood99, 1237–1245 (2002). | PubMed |
FURTHER READING Sallusto, F et al. The role of chemokine receptors in primary, effector, and memory immune responses. Annu. Rev. Immunol.18, 593–620 (2000). | PubMed |
