title: The proatherogenic role of T cells requires cell division and is dependent on the stage of the disease.
abstract: OBJECTIVE
  The mechanism by which T cells exert a proatherogenic potential is unclear. In order to determine whether this potential requires their replication, we crossed atherosclerosis-prone apolipoprotein E knockout mice (ApoE degrees) with transgenic mice in which exclusive and conditional ablation of dividing T cells relies on their specific expression of the herpes simplex type 1 thymidine kinase (TK) suicide gene.
  
  
  RESULTS
  We first showed that conalbumin-immunized ApoE degrees TK mice mounted a significant immune response to the antigen that was fully and specifically blocked by an in vivo ganciclovir (GCV) treatment. Next, ApoE degrees TK mice and ApoE degrees mice were treated or not with GCV either during the first 4 weeks (GCV 1 to 4w), the last 4 weeks (GCV 5 to 8w), or during 8 weeks (GCV 1 to 8w). Strikingly, ApoE degrees TK mice displayed a dramatic decrease in lesion development in the GCV 1 to 8w and GCV 5 to 8w groups, whereas the GCV had no effect when administered during the first 4 weeks. In protected mice, the inflammatory parameters in lesions, the percentage of CD69+ CD3+ splenocytes, and the circulating natural killer T cells were reduced.
  
  
  CONCLUSIONS
  The present study, therefore, shows that the proatherogenic potential of T cells is crucial in the progression of fatty streaks to mature plaques and requires cell division.
authors.affiliation: INSERM U681, Institut des Cordeliers/Université Paris 6 UPMC, Paris, France.
authors.forename: Jamila
authors.initials: J
authors.lastname: Khallou-Laschet
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Caligiuri
authors.forename: Emilie
authors.initials: E
authors.lastname: Groyer
authors.forename: Emanuel
authors.initials: E
authors.lastname: Tupin
authors.forename: Anh-Thu
authors.initials: AT
authors.lastname: Gaston
authors.forename: Bruno
authors.initials: B
authors.lastname: Poirier
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kronenberg
authors.forename: José L
authors.initials: JL
authors.lastname: Cohen
authors.forename: David
authors.initials: D
authors.lastname: Klatzmann
authors.forename: Srini V
authors.initials: SV
authors.lastname: Kaveri
authors.forename: Antonino
authors.initials: A
authors.lastname: Nicoletti
mesh_terms: D000818:Animals; D000998:Antiviral Agents; D001011:Aorta / Q000276:immunology / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000276:immunology* / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D018450:Disease Progression; D005260:Female; D015774:Ganciclovir; D015870:Gene Expression / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000235:genetics; D007694:Killer Cells, Natural / Q000473:pathology / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000473:pathology* / Q000502:physiology*; D013937:Thymidine Kinase / Q000235:genetics; D019076:Transgenes / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D001057:Apolipoproteins E; D013937:Thymidine Kinase; D015774:Ganciclovir