Diverse alterations in atherogenesis in hyperlipidemic CD4 and CD8 gene deficient mice

Abstract

Canada M4X1K9. T cells are prominent components of atherosclerotic lesions and many of them are activated and secreting cytokines. We have previously demonstrated an inhibition of atherogenesis CD4+ T cell ablated or nude C57BL/6 hyperlipidemic mice (Emeson et al, FACES J. 7, A490, 1993). In contrast, other investigators have presented evidence in rodents that T cells are not essential for the development of atherosclerosis or the vascular response to injury. Given the conflicting data and the importance of understanding the contribution of T cells in atherogenesis we have studied hyperlipidemic C57BL/6 mice with their CD4 or CDS genes disrupted by homologous recombination. Although there were no differences in plasma lipids among the groups after 24 weeks on the high fat atherogenic diet, aortic lesions of CD4V- mice were less than 1/3 the size of those of wild type controls. In contrast, lesions of CD8'/mice were larger than those of wild type controls. This study is among the first to presents genetic evidence that T cells play a role in the pathogenesis of early atherosclerotic lesions. It remains to be determined if similar mechanisms are operative in the pathogenesis of atherosclerosis in other animal models, in humans and in the progression of the fatty streak to more advanced lesions.