Adaptive immunity in atherogenesis: new insights and therapeutic approaches
Andrew H. Lichtman, … , Sotirios Tsimikas, Joseph L. Witztum
Andrew H. Lichtman, … , Sotirios Tsimikas, Joseph L. Witztum
Published January 2, 2013
Citation Information: J Clin Invest. 2013;123(1):27-36. https://doi.org/10.1172/JCI63108.
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Adaptive immunity in atherogenesis: new insights and therapeutic approaches

Abstract

Many remarkable advances have improved our understanding of the cellular and molecular events in the pathogenesis of atherosclerosis. Chief among these is the accumulating knowledge of how the immune system contributes to all phases of atherogenesis, including well-known inflammatory reactions consequent to intimal trapping and oxidation of LDL. Advances in our understanding of the innate and adaptive responses to these events have helped to clarify the role of inflammation in atherogenesis and suggested new diagnostic modalities and novel therapeutic targets. Here we focus on recent advances in understanding how adaptive immunity affects atherogenesis.

Authors

Andrew H. Lichtman, Christoph J. Binder, Sotirios Tsimikas, Joseph L. Witztum

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Figure 1

Theoretical events in initiation and effector phases of a proatherogenic T cell response.

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Theoretical events in initiation and effector phases of a proatherogenic...
Modified self-proteins generated in early atherosclerotic lesions (or systemically), such as the oxidatively modified apoB-100 component of LDL, are processed by DCs and presented as peptide/MHC complexes to naive T cells in secondary lymphoid tissues, leading to T cell clonal expansion and differentiation into effector T cells, such as Th1 or Th17 cells. The effector T cells migrate into arterial lesions, where resident macrophages or DCs present the same peptide-MHC antigens, leading to effector T cell activation and expression of pro-inflammatory effector molecules, such as secreted IFN-γ and IL-17 and membrane-bound CD40 ligand. These molecules promote lesion growth and/or destabilization.