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Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice
Giuseppina Caligiuri, … , Bruno Poirier, Göran K. Hansson
Giuseppina Caligiuri, … , Bruno Poirier, Göran K. Hansson
Published March 15, 2002
Citation Information: J Clin Invest. 2002;109(6):745-753. https://doi.org/10.1172/JCI7272.
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Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice

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Abstract

Atherosclerosis is characterized by vascular inflammation and associated with systemic and local immune responses to oxidized LDL (oxLDL) and other antigens. Since immunization with oxLDL reduces atherosclerosis, we hypothesized that the disease might be associated with development of protective immunity. Here we show that spleen-associated immune activity protects against atherosclerosis. Splenectomy dramatically aggravated atherosclerosis in hypercholesterolemic apoE knockout (apoE°) mice. Transfer of spleen cells from atherosclerotic apoE° mice significantly reduced disease development in young apoE° mice. To identify the protective subset, donor spleen cells were divided into B and T cells by immunomagnetic separation before transfer. Protection was conferred by B cells, which reduced disease in splenectomized apoE° mice to one-fourth of that in splenectomized apoE° controls. Protection could also be demonstrated in intact, nonsplenectomized mice and was associated with an increase in antibody titers to oxLDL. Fewer CD4+ T cells were found in lesions of protected mice, suggesting a role for T-B cell cooperation. These results demonstrate that B cell–associated protective immunity develops during atherosclerosis and reduces disease progression.

Authors

Giuseppina Caligiuri, Antonino Nicoletti, Bruno Poirier, Göran K. Hansson

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Figure 4

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Long-term survival of transferred lymphocytes. (a) Kinetics of PCR react...
Long-term survival of transferred lymphocytes. (a) Kinetics of PCR reactions for GAPDH and TK. The numbers of cycles chosen for semiquantitative analysis are indicated. (b) Spleen cells of mice expressing TK under the CD4 promoter were injected into sham-operated (black bars) or splenectomized (white bars) recipients. Four weeks later, homing of transferred cells was assessed by PCR analysis of the TK gene in DNA extracts (reflecting infiltrating donor cells) and RT-PCR analysis of TK mRNA in RNA extracts (reflecting infiltrating T cells) of different organs. TK RT-PCR data were normalized to GAPDH mRNA levels determined by RT-PCR (mean ± SEM, n = 4 mice per group). M, mesenteric; P+I, para-aortic and inguinal; LN, lymph nodes.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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Referenced in 11 patents
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