CD4+CD28- T lymphocytes contribute to early atherosclerotic damage in rheumatoid arthritis patients

Roberto Gerli, Giuseppe Schillaci, Andrea Giordano, Elena Bartoloni Bocci, Onelia Bistoni, Gaetano Vaudo, Simona Marchesi, Matteo Pirro, Federica Ragni, Yehuda Shoenfeld, Elmo Mannarino

Research output: Contribution to journalArticlepeer-review


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. Methods and 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-α led to a partial reappearance of the CD28 molecule on the CD4+ cell surface. Conclusions - Circulating CD4+CD28null 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-α 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.

Original languageEnglish
Pages (from-to)2744-2748
Number of pages5
Issue number22
StatePublished - 8 Jun 2004


  • Arthritis, rheumatoid
  • Cells
  • Endothelium
  • Vasodilation


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