Lymphocytes in early atherogenesis

In addition to their characteristic accumulation of macrophage-derived foam cells and proliferation of smooth muscle cells, atherosclerotic lesions contain T lymphocytes, predominantly of the Th1 class. Despite some evidence that these cells respond to epitopes that are found in the lesion, their role, if any, in the disease process has been hard to pin down. Song et al. have now revisited this question by following lesion progression in the atherosclerosis-prone LDLR-/- mouse strain, comparing LDLR-/-animals, which have a full complement of lymphocytes, with littermates of the double knockout genotype LDLR-/- RAG1-/- , which are devoid of B and T lymphocytes. The presence or absence of lymphocytes does not affect the ultimate outcome of feeding these mice a cholesterol-rich diet, but the authors find that the early events of lesion growth are slowed in double knockout mice. These findings are at odds with some earlier studies that examined the role of lymphocytes in pathogenesis in the ApoE-deficient strain, another widely studied atherosclerosis-prone model. Song et al. argue that their system more accurately matches human pathogenesis, in part because ApoE-deficiency (but not LDLR-deficiency) leads to impaired innate immune responses, a change that is not seen in humans with heart disease. Since RAG1-/- mice lack all lymphocytes, it will be important to examine the specific contributions of Th1 cells and other lymphocyte subtypes to this disease process.

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