Adoptive Transfer of β 2 -Glycoprotein I–Reactive Lymphocytes Enhances Early Atherosclerosis in LDL Receptor–Deficient Mice

Abstract

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 β 2 -glycoprotein I (β2GPI; a principal target of “autoimmune” antiphospholipid antibodies) enhances early atherosclerosis. In the present study, we tested the hypothesis that adoptive transfer of β2GPI-reactive T cells can accelerate fatty streak formation in LDL-RD mice. Methods and Results —LDL-RD mice were immunized with human β2GPI. An additional group of mice were immunized with β2GPI 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 β2GPI- or human serum albumin–immunized mice were stimulated in vitro with β2GPI 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 β2GPI-immunized animals displayed larger fatty streaks than those induced by control treated animals. T-cell–depleted splenocytes from β2GPI were unable to promote lesion formation in the mice. Conclusions —The present study provides the first direct evidence for a role of antigen (β2GPI)-reactive T cells in the promotion of fatty streaks in mice.