The pathogenesis of atherosclerotic disease is an incompletely understood, multifactorial process. It is clear that a combination of genetic and environmen-tal factors influence the development of the disease. Over the years, much attention has been focused on the contributions of abnormal lipid metabolism1 and vascular wall injury2, 3 to the atherosclerotic process. The hypothesis that immunological events also influ-ence atheromadevelopment mayseem a superflu-ous addition to an already complicated story. However, there is compelling evidence, discussed below (reviewed in Ref. 4), that T lymphocytes are a funda-mental component of the histopathology of early and late atherosclerotic lesions and that antibody responses to modified lipids found in atheromas are characteristic of the disease. Are these nonspecific immunological epiphenomena or, to the contrary, do specific immune responses influence the develop-ment and phenotype of atherosclerotic lesions? To date, the best wayto address the role of the immune system in pathological processes is with the use of experimental animals with well characterized immune systems. For molecular and cellular immunologists, inbred strains of mice have proved to be enormously useful and relevant tools for the study of immune responses in vivo. More recently, mouse models of atherosclerosis have been developed that faithfully recapitulate many of the characteristics of human disease. In this issue of The Journal, Zhou et al5 report that T lymphocyte infiltration and activation also occur within the atherosclerotic lesions of one of these murine models of atherosclerosis. Thisimpor-tant observation establishes the experimental link between mouse immunology and mouse atheroscle-rosis. This link is needed to answer the fundamental questions about the importance of immune responses to atherosclerotic vascular disease. Human atherosclerotic lesions consistently con-tain macrophages and T lymphocytes, two cell types that interact with each otherto promote cell-mediated immune responses. 6 6 Monocyte infiltration into early fatty streaks and foam cell transformation of these cells by lipid accumulation are well established events during the life history of atherosclerotic lesion. 9 15 Macrophages can express class 11 major histocompatibility complex (MHC) molecules, co-stimulatory molecules suchas B7-1 and B7-2, and they can process and display antigenic peptides for recognition by CD4+ T cells. Because of these prop-erties, macrophages efficiently present antigen to, and activate, CD4+ T cells. 16 In addition to macro-phages, CD4+ and CD8+ T lymphocytes are present within fatty streaks. 15, 17-20 Abundant CD4+ T cells can also be found in more advancedcarotid, coronary, and aortic lesions throughout the diseased vessel walls. 1521 The majority of these T cells have surface markers indicative of a memory pheno-type, 22 and analysis of T cell receptor gene usage indicates they are polyclonal. 23 The concurrence of macrophages and CD4+ T cells in atherosclerotic lesions suggests that the macrophage may present antigen to the T lymphocyte within the vessel wall and that T-lymphocyte-derived cytokines may acti-vate the macrophage. It could be argued that the presence of T lymphocytes within atheromas may reflect a nonspecific recruitment of these cells due to the up-regulation of adhesion molecules such as VCAM-1 and ICAM-1 on atheroma-associated endo-