Deleting TCR alpha beta+ or CD4+ T lymphocytes leads to opposite effects on site-specific atherosclerosis in female apolipoprotein E-deficient mice.
Recent studies have demonstrated the importance of lymphocytes, especially CD4(+) T cells, in early lesions of atherosclerosis in hypercholesterolemic mice. However, the role of other T cell subpopulations, like CD8(+) T cells or TCR gamma delta T lymphocytes, is not yet clear. We have therefore generated apolipoprotein E-deficient mice genetically deficient in specific T lymphocyte subpopulations and measured atherosclerotic lesions in the aortic sinus and en face whole aorta preparation at 18 weeks and at 1 year of age. Whereas TCR gamma delta(+) T lymphocytes appeared to play a modest role, TCR alpha beta(+) T lymphocytes played a major role as their deficiency significantly prevented early and late atherosclerosis at all arterial sites. However, neither CD4(+) nor CD8(+) T cells induced any significant decrease of the lesions at the aortic sinus, suggesting that compensatory proatherogenic mechanisms are operating at this site. Interestingly, the absence of CD4(+) T cells led to a dramatic increase in early lesion abundance at the level of the descending thoracic and abdominal aorta, which was still obvious at 1 year. In conclusion, whereas the TCR alpha beta(+) lymphocyte subset in its whole contribute to aggravate both early and late atherosclerosis, the CD4(+) T subpopulation appears to be critically protective at the level of the lower part of the aorta.
Elhage
Rima
R
INSERM U589, Institut L. Bugnard, 1 avenue Jean Poulhès, 31403 Toulouse Cédex, France.
Gourdy
Pierre
P
Brouchet
Laurent
L
Jawien
Jacek
J
Fouque
Marie-José
MJ
Fiévet
Catherine
C
Huc
Xavier
X
Barreira
Yara
Y
Couloumiers
Jean Claude
JC
Arnal
Jean-François
JF
Bayard
Francis
F
D000818:Animals; D001011:Aorta; D001057:Apolipoproteins E / Q000172:deficiency*; D001161:Arteriosclerosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D003433:Crosses, Genetic; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*
D001057:Apolipoproteins E; D008055:Lipids; D016693:Receptors, Antigen, T-Cell, alpha-beta