Adoptive transfer of beta(2)-glycoprotein I-reactive lymphocytes enhances early atherosclerosis in LDL receptor-deficient mice.
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 beta(2)-glycoprotein I (beta2GPI; a principal target of "autoimmune" antiphospholipid antibodies) enhances early atherosclerosis. In the present study, we tested the hypothesis that adoptive transfer of beta2GPI-reactive T cells can accelerate fatty streak formation in LDL-RD mice.


RESULTS
LDL-RD mice were immunized with human beta2GPI. An additional group of mice were immunized with beta2GPI 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 beta2GPI- or human serum albumin-immunized mice were stimulated in vitro with beta2GPI 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 beta2GPI-immunized animals displayed larger fatty streaks than those induced by control treated animals. T-cell-depleted splenocytes from beta2GPI were unable to promote lesion formation in the mice.


CONCLUSIONS
The present study provides the first direct evidence for a role of antigen (beta2GPI)-reactive T cells in the promotion of fatty streaks in mice.
George
J
J
Research Unit of Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv, Israel.
Harats
D
D
Gilburd
B
B
Afek
A
A
Shaish
A
A
Kopolovic
J
J
Shoenfeld
Y
Y
D019264:Adoptive Transfer; D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001161:Arteriosclerosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011973:Receptors, LDL / Q000172:deficiency / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D053482:beta 2-Glycoprotein I
D000906:Antibodies; D016207:Cytokines; D006023:Glycoproteins; D011973:Receptors, LDL; D053482:beta 2-Glycoprotein I; D002784:Cholesterol