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ß+ or CD4+ T Lymphocytes Leads to Opposite Effects on Site-Specific Atherosclerosis in Female Apolipoprotein E-Deficient Mice
From INSERM U589,* Animal Resources, Institut L. Bugnard, Toulouse Cédex; INSERM U545, Institut Pasteur, Lille Cédex, France; and the Center for Molecular Medicine and Department of Medicine, Karolinska Institute, Stockholm, Sweden
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
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+ T lymphocytes appeared to play a modest role, TCR
ß+ 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 TCRß+ 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.
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