Cellular and humoral immune responses to heat shock protein 65 are both involved in promoting fatty-streak formation in LDL-receptor deficient mice.
OBJECTIVE
This study was designed to determine the role of cellular and humoral immune responses to heat shock protein 65 (HSP65) in murine atherosclerosis.


BACKGROUND
Inflammatory processes appear to influence the progression of atherosclerosis. Immunization with HSP65 was previously shown to induce arteriosclerosis in rabbits and to enhance fatty-streak formation in mice. However, 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 immunized with HSP65 or control bovine serum albumin (BSA). Lymph-node cells, splenocytes 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 fatty-streak formation in comparison with mice treated with BSA-primed cells. Similarly, transfer of splenocytes reactive with HSP65 led to enhanced fatty-streak generation compared with mice injected with BSA-sensitized splenocytes. Repeated intraperitoneal administration of IgG from serum of HSP65-immunized mice (every 10 days) enhanced fatty-streak formation in mice in comparison with their anti-BSA-IgG injected littermates.


CONCLUSIONS
Antibodies and lymphocytes reactive to HSP65 promote fatty-streak formation in mice, providing direct evidence for the proatherogenic properties of cellular and humoral immunity to HSP65.
George
J
J
Department of Cardiology and the Cardiovascular Research Laboratory, Tel Aviv Medical Center, Tel Aviv, Israel.
Afek
A
A
Gilburd
B
B
Shoenfeld
Y
Y
Harats
D
D
D000818:Animals; D000917:Antibody Formation; D001161:Arteriosclerosis / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011973:Receptors, LDL / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D001426:Bacterial Proteins; D018834:Chaperonin 60; D007074:Immunoglobulin G; D011973:Receptors, LDL; D019010:Vascular Cell Adhesion Molecule-1; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins