Increased CD8(+) T cells associated with Chlamydia pneumoniae in symptomatic carotid plaque.

Abstract

The presence of Chlamydia pneumoniae has been reported in carotid atheroma, but its causative effect in the activation of an atherosclerotic plaque to a prothrombotic state remains unproved. Antigen- mediated activation of T lymphocytes within plaque may represent a mechanism by which infection can result in plaque conversion. The goal of the present study was to characterize the T-cell subtype profile related to the presence of C pneumoniae in patients with symptomatic versus asymptomatic carotid atherosclerosis. We studied 14 plaques (5 symptomatic and 9 asymptomatic) positive for C pneumoniae confirmed by polymerase chain reaction and 14 plaques (6 symptomatic and 8 asymptomatic) from age- and stenosis-matched patients negative for C pneumoniae by polymerase chain reaction. T-cell subpopulations of T-helper, T-cytotoxic, and T-memory lymphocytes were identified through indirect enzyme immunohistochemistry with anti-CD3+, anti-CD4+, anti-CD8+, and anti-CD45RO+ monoclonal antibodies, respectively. Results are expressed as the number of positive cells per millimeter squared. In the absence of C pneumoniae, symptomatic plaques had a modest but significant increase of CD3+ (89.6 versus 55.3, P=0.013), CD4+ (57.3 versus 32.7, P=0.01), and CD45RO+ (82.8 versus 43.7, P=0.007), but not CD8+ T cells (28.5 versus 25.5, P=0.245) compared with asymptomatic. However, in the presence of C pneumoniae, there was significant increase of all T-lymphocyte subtypes in symptomatic plaques, including CD8+ (76.8 versus 30.3, P=0.03), CD3+ (192.1 versus 80.4, P=0.004), CD4+ (111.9 versus 37.9, P=0.003), and CD45RO+ (120.2 versus 72.9, P=0.003) cells compared with asymptomatic plaques. With use of 2-way ANOVA, both the presence of chlamydia and symptoms were associated with significantly higher T-cell counts (P<0.005 for all subtypes). Although all patients with symptomatic disease show a modest elevation in the concentration of intraplaque lymphocytes, a preferential increase in CD8+ class I-restricted T cells is observed in symptomatic carotid plaque positive for C pneumoniae. These data provide incentive to further explore the role of Chlamydia in the modification of immune-mediated mechanisms in active atherosclerotic plaque.