title: The intensity of immune activation is linked to the level of  CCR5 expression in human immunodeficiency virus type  1-infected persons.
abstract: Immune activation is a main driver of AIDS- and non-AIDS-linked morbidities in the course of HIV-1 infection. As CCR5, the main HIV-1 co-receptor, is not only a chemokine receptor but also a co-activation molecule expressed at the surface of T cells, it could be directly involved in this immune activation. To test this hypothesis, we measured by flow cytometry the mean number of CCR5 molecules at the surface of non-activated CD4(+) T cells (CCR5 density), which determines the intensity of CCR5 signalling, and the percentage of CD8(+) T cells over-expressing CD38 (CD38 expression), a major marker of immune activation, in the blood of 67 HIV-1-infected, non-treated individuals. CCR5 density was correlated with CD38 expression independently of viral load (P=0.016). CCR5 density remained unchanged after highly active anti-retroviral therapy (HAART) introduction or cessation, whereas CD38 expression decreased and increased, respectively. Moreover, pre-therapeutic CCR5 density was highly predictive (r=0.736, P<10(-4) ) of residual CD38 over-expression after 9 months of HAART. Hence, CCR5 might play an immunological role in HIV-1 infection as a driver of immune activation. This could explain why CCR5 antagonists may have an inhibitory effect on immune activation.
authors.affiliation: Département d'Immunologie, CHU de Montpellier, Université Montpellier 1, Montpellier, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Portales
authors.forename: Katerina Christina
authors.initials: KC
authors.lastname: Psomas
authors.forename: Edouard
authors.initials: E
authors.lastname: Tuaillon
authors.forename: Thibault
authors.initials: T
authors.lastname: Mura
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vendrell
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Eliaou
authors.forename: Jacques
authors.initials: J
authors.lastname: Reynes
authors.forename: Pierre
authors.initials: P
authors.lastname: Corbeau
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis*; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D008213:Lymphocyte Activation; D019713:Receptors, CCR5 / Q000276:immunology* / Q000378:metabolism*; D053218:Receptors, Death Domain / Q000378:metabolism; D019562:Viral Load
chemical_list: D019713:Receptors, CCR5; D053218:Receptors, Death Domain; D051997:ADP-ribosyl Cyclase 1