Detection of Chlamydia pneumoniae –Reactive T Lymphocytes in Human Atherosclerotic Plaques of Carotid Artery

Abstract

Abstract-Linkage between Chlamydia pneumoniae infection and atherosclerosis has been confirmed in several studies, but the precise role of this organism in the disease process is not known. We investigated the relation and reactivity of T lymphocytes of human carotid plaques to C pneumoniae antigens. Tissue specimens were obtained from 17 patients who underwent carotid endarterectomy. Immunohistological staining and/or in situ hybridization revealed the presence of C pneumoniae in 11 (64%) of the 17 of the cases. Inflammatory infiltration seen in the vessel walls consisted primarily of CD45ROϩ T-memory lymphocytes (median 80%, range 50% to 90%), whereas CD20ϩ B cells and monocytes were in minor proportion. In vivo activated T lymphocytes were propagated from the specimens with interleukin-2, and the antigen specificity of the established T-cell lines (TLLs) was analyzed against C pneumoniae elementary body antigen. TLLs were established from all 17 carotid tissues but none from the control specimens of ascending aorta. C pneumoniae was recognized as a specific T-cell-stimulating antigen in 7 (41%) of 17 cases. Further analyses of the C pneumoniae-reactive TLLs showed that chlamydial 60-kDa heat-shock protein induced specific proliferation in 5 (71%) of 7 cases and revealed 2 haplotype (DRB1*1502 and DQB1*06) binding motifs in human 60-kDa heat-shock protein. C pneumoniae was identified as a specific microbial antigen recognized by 41% of TLLs propagated from in vivo activated plaque T cells. Our results suggests that cell-mediated immunity to C pneumoniae plays a role in the atherosclerotic process and that this response may involve autoimmunity. (Arterioscler Thromb Vasc

Association of HLA-DRB3*0202 and serum IgG antibodies to Chlamydia pneumoniae with essential hypertension in a highly homogeneous population from Majorca (Balearic Islands, Spain)

“…However, these initial findings may help to elucidate in further studies mechanisms for development of EH. Since the interaction in the risk for EH of one allele of the HLA system (a key element of the immune response) and an infectious agent (C. pneumoniae) has been described in our study, the probability that immune and inflammatory mechanisms are important factors in the pathogenesis of EH (as has been well documented in atherosclerosis at the cellular 21 and biochemical level 22 ) is clearly higher than that previously suspected. On the basis of several experimental findings, [23][24][25][26][27][28] it has been hypothesized that chronic C. pneumoniae infection of the vessels may induce a chronic immune response orchestrated by cytokines and mediated by reactive oxygen intermediates.…”

T helper type 1 lymphocytes drive inflammation in human atherosclerotic lesions

“…With a similar approach, Stemme et al (41) succeeded in isolating a plaque-derived CD4 ϩ clones specific to oxidized low-density lipoprotein. In contrast, other investigators used repeated stimulation with C. pneumoniae antigens and mitogens to expand plaque-infiltrating T cells, increasing the risk of in vitro artifacts in their analysis (42,43). Our data on the fine specificity of plaque-derived C. pneumoniae-specific clones showed a precise antigenic role for chlamydial OMP-2, HSP-10, and HSP-60.…”

Heat-Shock Protein 60-Reactive CD4 + CD28 null T Cells in Patients With Acute Coronary Syndromes

“…[21][22][23][24][25][26] The finding of CD4 ϩ CD28 null cells reactive to hHSP60 during the acute phase of coronary artery disease and their absence in stable CSA and healthy individuals is of critical importance and suggests that an autoimmune T cell-mediated response may hold the balance. Although previous studies have reported the presence of HSP-reactive T cells within atheromatous lesions, 8 this is the first investigation into antigenic specificity of the CD4 ϩ CD28 null cells. The mechanism of emergence and outgrowth of these cells is unknown.…”