The role of CC chemokine receptor 5 in antiviral immunity
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The role of CC chemokine receptor 5 in antiviral immunity. / Nansen, Anneline; Christensen, Jan Pravsgaard; Andreasen, Susanne Ørding; Bartholdy, Christina; Christensen, Jeanette Erbo; Thomsen, Allan Randrup.
In: Blood, Vol. 99, No. 4, 2002, p. 1237-45.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The role of CC chemokine receptor 5 in antiviral immunity
AU - Nansen, Anneline
AU - Christensen, Jan Pravsgaard
AU - Andreasen, Susanne Ørding
AU - Bartholdy, Christina
AU - Christensen, Jeanette Erbo
AU - Thomsen, Allan Randrup
N1 - Keywords: Animals; Antigens, Viral; Chemotaxis, Leukocyte; Disease Models, Animal; Immunity; Lymphocyte Activation; Lymphocytic Choriomeningitis; Meningitis, Viral; Mice; Mice, Knockout; Receptors, CCR5; T-Lymphocyte Subsets; Virus Diseases
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
M3 - Journal article
C2 - 11830471
VL - 99
SP - 1237
EP - 1245
JO - Blood
JF - Blood
SN - 0006-4971
IS - 4
ER -
ID: 9639417