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(Circulation Research. 2002;90:1039.)
© 2002 American Heart Association, Inc.

Editorials

T Lymphocytes in Atherosclerosis

The Yin-Yang of Th1 and Th2 Influence on Lesion Formation

Alan Daugherty, Debra L. Rateri

From the Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, Lexington, Ky.

Correspondence to Alan Daugherty, PhD, Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, Lexington, KY 40536-0230. E-mail adaugh@uky.edu

Key Words: atherosclerosis • interleukins

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)- 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 includes the detection of IFN- mRNA and protein in lesions.^5,6 A direct role in . . . [Full Text of this Article]

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