Evidence for the involvement of T cell costimulation through the B-7/CD28 pathway in atherosclerotic plaques from apolipoprotein E knockout mice

Arnon Afek, Dror Harats, Arie Roth, Gad Keren, Jacob George

Research output: Contribution to journalArticlepeer-review

Abstract

Antigen-specific T cell activation is thought to influence the initiation and progression of the atherosclerotic plaque. For the T cell activation program to be functional, it is essential not only to facilitate T cell receptor engagement by antigen-presenting cells (APC), but also to deliver requisite costimulatory signals. The most widely comprehended costimulatory pathway involves the ligation of CD28 expressed on T cells by CD80 and CD86 upregulated on APCs. We hypothesized that signals of costimulation should be localized to plaque areas that correspond to the presence of the provoking autoantigen. Atherosclerotic plaques from apoE knockout (KO) mice at different stages of maturation were studied immunohistochemically by monoclonal antibodies to respective markers of primary and secondary lymphocyte activation. Subsequently, flow cytometry studies were conducted in spleen cells from C57BL/6 and apoE KO mice aiming to determine whether the presence of plaques is associated with increased expression of costimulatory signals. We found that regardless of the maturation stage, CD80 and CD86 were evident within the plaques, and colocalized with the presence of markers of dendritic cells and with expression of the extensively investigated autoantigen-oxidized LDL. FACS analysis studies showed that splenocytes from aged atherosclerotic apoE KO mice exhibited increased expression on B cells (which represent APCs) of CD80 and CD86 as compared to their young apoE or naïve C57BL/6 litters that have no plaques. These results suggest that primary T cell activation may assume a functional proinflammatory program within the plaque by involvement of CD28/B7 costimulatory pathway.

Original languageEnglish
Pages (from-to)219-223
Number of pages5
JournalExperimental and Molecular Pathology
Volume76
Issue number3
DOIs
StatePublished - Jun 2004

Keywords

  • Atherosclerosis
  • Immune system
  • Lymphocyte
  • Oxidized LDL

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