T Lymphocytes in Atherosclerosis
The Yin-Yang of Th1 and Th2 Influence on Lesion Formation
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The presence of activated T lymphocytes in all stages of human atherosclerotic lesion development implies their involvement in this vascular disease process.1 However, the specific role T lymphocytes play in atherogenesis remains unclear. It is not feasible to regulate the immune system in humans to determine its association with atherosclerotic-related diseases. Therefore, dissection of the role of T lymphocytes in lesion development will be dependent on animal models. Appropriate animal models need to mimic the cellular composition of human lesions, particularly in content of T lymphocytes. In this respect, the most commonly used mouse models of atherosclerosis, such as apolipoprotein E −/− and low-density lipoprotein (LDL) receptor −/− mice, contain T lymphocytes, although the number of cells is less than in human lesions.2 T-lymphocyte presence has functional consequences, because their complete absence reduces lesion formation during moderate hypercholesterolemia.3,4⇓
The major class of T lymphocytes present in atherosclerotic lesions is CD4+. In response to the local milieu of cytokines, CD4+ cells differentiate into the Th1 or Th2 lineage. Among the principal inducers of the Th1 and Th2 cells are interleukin (IL)-12 and IL-10, respectively. Activated T lymphocytes are functionally defined by the cytokines produced with interferon (IFN)-γ secreted from the Th1 cells and IL-4 from the Th2 cells.
Much of the emphasis in atherosclerosis research in relation to T lymphocytes has focused on the role of Th1-type responses. The evidence for the role of Th1 cells …