INHIBITION OF ATHEROSCLEROSIS IN CD4 T-CELL-ABLATED AND NUDE (NU NU) C57BL/6 HYPERLIPIDEMIC MICE/

T lymphocytes and monocyte/macrophages are prominent components of ath erosclerotic lesions, and many of these cells are activated and secret ing cytokines. To determine the role of these cells in the pathogenesi s of athersclerosis, we studied its development in T-cell-deficient mi ce fed a high fat atherogenic diet Depleting euthymic mice of their CD 4(+) lymphocytes by 20 weekly injections of CD4 monoclonal antibodies reduced the mean area of their aortic lesions by approximately 70%. Si milarly, the mean lesion area of T-cell-deficient nude (nu/nu) mice wa s 10% of the size of that of their heterozygote (nu/+) litter mates. F low cytometric studies of splenic T cells and analyses of serum total and HDL cholesterol of these mice indicated that the differences in me an lesion areas among the experimental groups were most closely correl ated with differences in splenic T cell content. These studies suggest that in these two models T lymphocytes contribute to the pathogenesis of early atherosclerotic lesions and that a further understanding of this phenomenon may provide future approaches toward the prevention an d treatment of the disease.