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Analysis of the T-cell receptor repertoire in human atherosclerosis
J R Oksenberg1, G T Stavri, M C Jeong
1Department of Neurology, School of Medicine, University of California at San Francisco 94143-0435, USA.
Objective:
Analysis of T-cell receptor (TCR) beta-chain gene expression in atherosclerotic lesions of human aorta.
Methods:
TCR diversity was studied using non-radioactive polymerase chain reaction for quantitative assessment of TCRBV gene transcripts, together with size and sequence analysis of the beta-chain third complementarity-determining region (CDR3). Samples represent a wide range of atheromatous histology, allowing evaluation of the T-cell repertoire at different stages of disease.
Results:
Diverse TCRBV family usage was observed in the majority of the samples, as the 25 different TCRBV products were detected at levels exceeding background. The data also showed that TCRBV transcripts expressed in the diseased aorta tissue displayed considerable size heterogeneity and no repetition of CDR3 nucleotide motifs.
Conclusions:
The early presence of T-lymphocytes in the atheromatous blood vessel has been interpreted as an indication of specific immunological reactions operating during the course of the atherosclerotic process. Although a T-cell infiltrate characterized by limited usage of TCRAV genes cannot be excluded the unrestricted usage of TCRBV genes argues against a local T-cell clonal expansion in atherogenesis.