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Oxidized LDL induces changes in several facets of the immune system, although the relationships between these facets and their contributions to atherogenesis have yet to be fully elucidated. A report in this issue of the JCI provides a novel demonstration of the adaptive immune system influencing the production of natural antibodies. The results demonstrate that injection of malondialdehyde-modified LDL promotes a Th2 response that in turn increases the titers of the natural antibody T15/EO6, which recognizes the oxidized phospholipid POVPC. Atherosclerotic lesion size in LDL receptor-deficient mice is reduced as a consequence of the increase in natural antibody titers, and IL-5 is identified as the link between the adaptive and natural immune systems (see related article beginning on page 427).