title: Induction of T helper 2 responses against human apolipoprotein B100 does not affect atherosclerosis in ApoE-/- mice.
abstract: OBJECTIVE
  Immune responses against LDL antigens have been found to play an important modulatory role in atherosclerosis. Immunization with homologous oxidized LDL, as well as human apolipoprotein B100 (ApoB)-derived peptides, inhibits atherosclerosis in hypercholesterolaemic animal models of atherosclerosis. However, the role of antigen-specific T helper 2 (Th2) responses in atherosclerosis remains to be fully clarified.
  
  
  RESULTS
  ApoE(-/-) mice on high-fat diet were immunized with human ApoB using Alum as an adjuvant at 12, 14, and 16 weeks of age. Alum-injected and non-treated mice were used as controls. At 17 weeks of age, a matrigel plug containing ApoB was placed subcutaneously and T-cell infiltration into the plug as well as the development of aortic root atherosclerotic lesions were analysed after an additional 7 days. Immunization with ApoB resulted in four-fold increased accumulation of effector T cells in ApoB-containing matrigel when compared with control groups. The levels of the Th2 cytokines IL-4, IL-5, and IL-10 were also increased in ApoB-containing matrigel plugs. Moreover, the levels of Th2-associated IgG1 against human and also mouse LDL were increased in the plasma of ApoB-immunized mice. In spite of the induction of a Th2 response partially reacting also with the endogenous LDL, there was no difference in atherosclerosis when compared with the Alum group.
  
  
  CONCLUSIONS
  This study describes a novel model to study antigen-specific T-cell responses in vivo in mouse models of atherosclerosis. The results suggest that activation of Th2 immunity does not mediate the protective effect of immunization with LDL antigens described previously.
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö University Hospital, CRC 60:13, Jan Waldenströms gata 35, 20502 Malmö, Sweden daniel.engelbertsen@med.lu.se.
authors.forename: Daniel
authors.initials: D
authors.lastname: Engelbertsen
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö University Hospital, CRC 60:13, Jan Waldenströms gata 35, 20502 Malmö, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Rattik
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö University Hospital, CRC 60:13, Jan Waldenströms gata 35, 20502 Malmö, Sweden.
authors.forename: Anki
authors.initials: A
authors.lastname: Knutsson
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö University Hospital, CRC 60:13, Jan Waldenströms gata 35, 20502 Malmö, Sweden.
authors.forename: Harry
authors.initials: H
authors.lastname: Björkbacka
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö University Hospital, CRC 60:13, Jan Waldenströms gata 35, 20502 Malmö, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Bengtsson
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö University Hospital, CRC 60:13, Jan Waldenströms gata 35, 20502 Malmö, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Nilsson
mesh_terms: D000818:Animals; D053299:Apolipoprotein B-100 / Q000276:immunology / Q000378:metabolism*; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism; D050197:Atherosclerosis / Q000276:immunology* / Q000473:pathology; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D006801:Humans; D008077:Lipoproteins, LDL / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*
chemical_list: D053299:Apolipoprotein B-100; D001057:Apolipoproteins E; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein
keywords: Atherosclerosis; Autoimmunity; Matrigel; T cells; Th2