The proatherogenic role of T cells requires cell division and is dependent on the stage of the disease.
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.
Khallou-Laschet
Jamila
J
INSERM U681, Institut des Cordeliers/Université Paris 6 UPMC, Paris, France.
Caligiuri
Giuseppina
G
Groyer
Emilie
E
Tupin
Emanuel
E
Gaston
Anh-Thu
AT
Poirier
Bruno
B
Kronenberg
Mitchell
M
Cohen
José L
JL
Klatzmann
David
D
Kaveri
Srini V
SV
Nicoletti
Antonino
A
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
D000998:Antiviral Agents; D001057:Apolipoproteins E; D013937:Thymidine Kinase; D015774:Ganciclovir