THE EFFECTS OF TOTAL LYMPHOCYTE DEFICIENCY ON THE EXTENT OF ATHEROSCLEROSIS IN APOLIPOPROTEIN E- -MICE/

Activated T lymphocytes are present in human atherosclerotic lesions a nd autoantibodies to antigens within lesions have been detected in ser um, but the roles of the cellular and humoral immune systems in athero genesis have not been determined. The effect of total lymphocyte defic iency on atherogenesis was investigated by crossing apo E-deficient mi ce (which develop atherosclerosis resembling human disease) with mice deficient in RAG2 (which is required for normal B and T lymphocyte dev elopment). Mice were placed on a fat-and choIesterol-enriched diet for 12 wk. RAG2-defrcient mice had no serum autoantibodies, in contrast t o the high titers in RAG2+/- littermates. There were no T lymphocytes and a markedly reduced number of MI-IC class II-positive macrophages i n atherosclerotic lesions of RAG2-deficient mice. Despite these differ ences, RAG2-deficient mice developed atherosclerosis similar in extent to that in immunocompetent littermates, based on quantification by tw o independent methods. In conclusion, the absence of autoantibodies an d T lymphocytes did not influence the extent of aortic atherosclerotic lesions in apo E-deficient mice.