Cellular and humoral immune responses to heat shock protein 65 are both involved in promoting fatty-streak formation in LDL-receptor deficient mice

OBJECTIVES This study was designed to determine the role of cellular and hu moral immune responses to heat shock protein 65 (HSP65) in murine atheroscl erosis. BACKGROUND Inflammatory processes appear to influence the progression of at herosclerosis. Immunization with HSP65 was previously shown to induce arter iosclerosis in rabbits and to enhance fatty-streak formation in mice. Howev er, it has not been demonstrated directly whether HSP65-reactive antibodies and lymphocytes are separately capable of influencing lesion formation. METHODS Low density lipoprotein-receptor deficient (LDL-RD) mice were immun ized with HSP65 or control bovine serum albumin (BSA). Lymph-node cells, sp lenocytes and immunoglobulin G (IgG) were obtained from the immunized mice and transferred separately to six groups of syngenic LDL-RD mice. RESULTS Adoptive transfer of HSP65-reactive lymph node cells increased fatt y-streak formation in comparison with mice treated with BSA-primed cells. S imilarly, transfer of splenocytes reactive with HSP65 led to enhanced fatty -streak generation compared with mice injected with BSA-sensitized splenocy tes. Repeated intraperitoneal administration of IgG from serum of HSP65-imm unized mice (every 10 days) enhanced fatty-streak formation in mice in comp arison with their anti-BSA-IgG injected littermates. CONCLUSIONS Antibodies and lymphocytes reactive to HSP65 promote fatty-stre ak formation in mice, providing direct evidence for the proatherogenic prop erties of cellular and humoral immunity to HSP65. (C) 2001 by the American College of Cardiology.