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(Circulation. 2000;102:1822.)
© 2000 American Heart Association, Inc.

Basic Science Reports

Adoptive Transfer of ß₂-Glycoprotein I–Reactive Lymphocytes Enhances Early Atherosclerosis in LDL Receptor–Deficient Mice

Jacob George, MD¹; Dror Harats, MD¹; Boris Gilburd, MD, PhD; Arnon Afek, MD; Aviv Shaish, PhD; Juri Kopolovic, MD; Yehuda Shoenfeld, MD

From the Research Unit of Autoimmune Diseases (J.G., B.G., Y.S.), Department of Medicine B, and Institutes of Pathology (A.A., J.K.) and Lipid and Atherosclerosis Research (D.H., A.S.), Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Correspondence to Yehuda Shoenfeld, MD, Department of Medicine B, Sheba Medical Center, Tel-Hashomer 52621, Israel. E-mail shoenfel{at}post.tau.ac.il

Background—It has been proposed that autoimmune factors can influence the progression of atherosclerosis. We have previously shown that immunization of LDL receptor–deficient (LDL-RD mice) with ß₂-glycoprotein I (ß2GPI; a principal target of "autoimmune" antiphospholipid antibodies) enhances early atherosclerosis. In the present study, we tested the hypothesis that adoptive transfer of ß2GPI-reactive T cells can accelerate fatty streak formation in LDL-RD mice.

Methods and Results—LDL-RD mice were immunized with human ß2GPI. An additional group of mice were immunized with ß2GPI and boosted with the same antigen 3 weeks later. Control mice with immunized with human serum albumin. Lymphocytes obtained from the draining lymph node cells or from splenocytes of ß2GPI- or human serum albumin–immunized mice were stimulated in vitro with ß2GPI or with the mitogen concavalin A, respectively. The cultured lymphocytes were transferred intraperitoneally to syngenic LDL-RD mice, and the mice were fed a high-fat "Western" diet for 5 weeks until death. Mice injected with lymphocytes from draining lymph nodes or spleens of ß2GPI-immunized animals displayed larger fatty streaks than those induced by control treated animals. T-cell–depleted splenocytes from ß2GPI were unable to promote lesion formation in the mice.

Conclusions—The present study provides the first direct evidence for a role of antigen (ß2GPI)-reactive T cells in the promotion of fatty streaks in mice.

Key Words: atherosclerosis • ß₂-glycoprotein • lymphocytes • mice • immunology system

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