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B cells treated with CTB-p210 acquire a regulatory phenotype in vitro and reduce atherosclerosis in apolipoprotein E deficient mice

Journal article
Authors S. Rattik
P. T. Mantani
I. Y. Mattisson
I. Ljungcrantz
L. Sundius
H. Bjorkbacka
Manuela Terrinoni
Michael Lebens
Jan Holmgren
J. Nilsson
M. Wigren
G. N. Fredrikson
Published in Vascular Pharmacology
Volume 111
Pages 54-61
ISSN 1537-1891
Publication year 2018
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Pages 54-61
Language en
Links dx.doi.org/10.1016/j.vph.2018.09.00...
Keywords Atherosclerosis, Regulatory B cells, Tolerance, Regulatory T cells, b-100 peptide sequences, t-cells, adoptive transfer, lymphocytes, immunization, antibodies, induction, tolerance, apo-b-100, subsets
Subject categories Immunology in the medical area

Abstract

Objective: Intranasal immunization with a fusion protein of the ApoB100-derived peptide p210 and the cholera toxin B subunit (CTB-p210) has previously been shown to induce mucosal tolerance and reduce atherosclerosis development, but the exact mode of action remains to be elucidated. Recent studies have indicated an important role for B cells in mucosal tolerance, in particular by induction of regulatory B (Bregs) and T cells (Tregs). In this study, we aimed to investigate if transfer of B cells pulsed with CTB-p210 can protect against atherosclerosis. Method and results: First, we studied if CTB-p210 can induce Bregs and Tregs in vitro. After pulsing B cells from Apob(tm2gy)ldlr(-/-) or Apoe(-/-) mice with CTB-p210 for 1 h and co-culturing them with naive T cells for 48 h, we observed increased expression of membrane bound TGF beta/latency-associated peptide (mTGF beta/LAP) on B cells and an increased proportion of CD25(hi)FoxP3(+) Tregs. Adoptive transfer of B cells pulsed with CTB-p210 into high-fat diet-fed Apoe(-/-) mice at 8, 10 and 12 weeks of age, reduced the plaque area in the aorta at 20 weeks of age as compared with control-treated (CTB-pOVA treated B cells or PBS) mice. Moreover, mice receiving p210-CTB treated B cells had increased levels of anti-p210 IgG antibodies. Conclusion: Our observations suggest that CTB-p210 pulsed B cells acquire a regulatory phenotype and induce Tregs in vitro. Adoptive transfer of CTB-p210, but not control-treated, B cells into Apoe(-/-) mice decreased atherosclerosis development.

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