Altered immune responses in apolipoprotein E-deficient mice

Apolipoprotein E (apoE) is a 34 kDa glycosylated protein with multiple biol ogical properties, In addition to its role in cholesterol transport, apoE h as in vitro immunomodulatory properties, Recent data suggest that these imm unomodulatory effects of apoE may be biologically relevant, and apoE-defici ent mice have altered immune responses after bacterial inoculation and incr eased susceptibility to endotoxemia induced by lipopolysaccharide (LPS), To better understand the mechanism by which apoE-modulates immune responses, we tested the role of human apoE isoforms in assays of human T cell prolife ration, and analyzed the immune responses of apoE-deficient mice, Both the E3 and E4 isoforms of apoE induced similar suppression of human lymphocyte function in assays of T cell proliferation, including mitogenic responses t o phytohaemagglutin (PHA), stimulation of the T cell receptor with alpha CD 3, and antigen-specific response to tetanus toroid, ApoE-deficient mice sho wed no quantitative differences in thymic, splenic, or bone marrow lymphocy te populations, nor were there in vitro abnormalities in splenocyte prolife ration after stimulation with alpha CD3 to suggest an inherent T cell defec t in apoE-deficient mice, ApoE deficient animals, however, had significantl y higher levels of antigen-specific IgM after immunization with tetanus tor oid, and impaired delayed type hypersensitivity responses as compared to co ntrol C57-BL/6 mice. These results support a growing body of evidence demon strating an interplay between lipid metabolism and immune responses, and su ggest that apoE plays a biologically relevant role in regulating humoral an d cell-mediated immunity.