title: CD4+CD28- T lymphocytes contribute to early atherosclerotic damage in rheumatoid arthritis patients.
abstract: BACKGROUND
  Peripheral blood expansion of an unusual CD4+ T-cell subset lacking surface CD28 has been suggested to predispose rheumatoid arthritis (RA) patients to develop more aggressive disease. However, the potential association between CD4+CD28null T cells and early atherosclerotic changes in RA has never been investigated.
  
  
  RESULTS
  The number of circulating CD4+CD28null cells was evaluated in 87 RA and 33 control subjects who also underwent evaluation of carotid artery intima-media thickness (IMT) and endothelial function via flow-mediated vasodilation (FMV). Patients had higher IMT and lower FMV compared with control subjects. The frequency of CD4+CD28null cells was significantly higher in patients than in control subjects. Twenty patients with persistent expansion of circulating CD4+CD28null cells had more marked increase of carotid artery IMT and stronger decrease of brachial artery FMV. Blockade of tumor necrosis factor-alpha led to a partial reappearance of the CD28 molecule on the CD4+ cell surface.
  
  
  CONCLUSIONS
  Circulating CD4+CD28(null) lymphocytes are increased in RA. Patients with persistent CD4+CD28null cell expansion show preclinical atherosclerotic changes, including arterial endothelial dysfunction and carotid artery wall thickening, more significantly than patients without expansion. These findings suggest a contribution of this cell subset in atheroma development in RA. Moreover, the demonstration that tumor necrosis factor-alpha blockade is able to reverse, at least in part, the CD28 deficiency on the CD4+ cell surface may be of interest for possible innovative therapeutic strategies in cardiovascular diseases.
authors.affiliation: Center for the Study of Rheumatic Diseases, Section of Internal Medicine and Oncological Sciences, Department of Clinical and Experimental Medicine, University of Perugia, Policlinico di Monteluce, I-06122 Perugia, Italy. gerlir@unipg.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Gerli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Schillaci
authors.forename: Andrea
authors.initials: A
authors.lastname: Giordano
authors.forename: Elena Bartoloni
authors.initials: EB
authors.lastname: Bocci
authors.forename: Onelia
authors.initials: O
authors.lastname: Bistoni
authors.forename: Gaetano
authors.initials: G
authors.lastname: Vaudo
authors.forename: Simona
authors.initials: S
authors.lastname: Marchesi
authors.forename: Matteo
authors.initials: M
authors.lastname: Pirro
authors.forename: Federica
authors.initials: F
authors.lastname: Ragni
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Shoenfeld
authors.forename: Elmo
authors.initials: E
authors.lastname: Mannarino
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001161:Arteriosclerosis / Q000209:etiology / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000000981:diagnostic imaging / Q000276:immunology* / Q000503:physiopathology; D018106:CD28 Antigens / Q000097:blood* / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology / Q000502:physiology*; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014463:Ultrasonography; D014664:Vasodilation / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab