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Blood, 15 February 2002, Vol. 99, No. 4, pp. 1237-1245
IMMUNOBIOLOGY
The role of CC chemokine receptor 5 in antiviral
immunity
Anneline Nansen,
Jan
Pravsgaard Christensen,
Susanne Ørding Andreasen,
Christina Bartholdy,
Jeanette Erbo Christensen, and
Allan Randrup Thomsen
From the Institute of Medical Microbiology and
Immunology, University of Copenhagen, Denmark.
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.
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