T lymphocyte lines isolated from atheromatous plaque contain cells capable of responding to Chlamydia antigens.
Chlamydia pneumoniae infection is associated with atherosclerosis and the organism has been identified in arterial lesions. To determine whether T lymphocyte-mediated immune responses to Chlamydia antigens within plaque could contribute to pathogenesis, we have derived T cell lines from atherosclerotic plaques of 32 patients. Culture with IL-2 alone proved insufficient for cellular activation and expansion, but additional stimulation with phytohaemagglutinin (PHA) or recall antigens allowed consistent establishment of T cell lines. Furthermore, in cultures of approx. 500 tissue fragments, Chlamydia organisms proved as effective as other recall antigens in producing outgrowth of arterial T cells (20-25% wells produced T cell lines). Testing the antigen responsiveness of T cell lines showed that those derived using Chlamydia organisms were more likely to respond to Chlamydia (5/29+) than those isolated using other stimuli (6/69+ for PHA; 5/57+ for PPD and tetanus toxoid (TT)). However, lines responsive to each of the recall antigens were observed. Using recombinant Chlamydia antigens, some Chlamydia-specific T cell lines were shown to respond to OMP2 and/or hsp60. Those recognizing Chlamydia hsp60 did not cross-react with human hsp60, but human hsp60-responsive lines were also observed. Thus, atherosclerotic plaque tissue contains a variety of memory T lymphocytes, and amongst these are cells capable of recognizing Chlamydia antigens. In a C. pneumoniae-infected plaque, such T cells may be activated by local antigen and could contribute to the inflammatory process in the arterial wall through CD40 ligand expression and cytokine secretion.
Departments of Medicine and Neurosurgery, University of Cambridge, Cambridge, UK.
A J
AJ
Curry
I
I
Portig
J C
JC
Goodall
P J
PJ
Kirkpatrick
J S
JS
Gaston
D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000276:immunology*; D001161:Arteriosclerosis / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D002460:Cell Line; D018834:Chaperonin 60 / Q000276:immunology; D002690:Chlamydia Infections / Q000150:complications; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D004357:Drug Synergism; D016894:Endarterectomy, Carotid; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000473:pathology*
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D018834:Chaperonin 60; D007376:Interleukin-2; D010835:Phytohemagglutinins