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

• Published in: Circulation (New York, N.Y.) N.Y.), 2004-06, Vol.109 (22), p.2744-2748
• Main Authors: GERLI, Roberto, SCHILLACI, Giuseppe, MANNARINO, Elmo, GIORDANO, Andrea, BOCCI, Elena Bartoloni, BISTONI, Onelia, VAUDO, Gaetano, MARCHESI, Simona, PIRRO, Matteo, RAGNI, Federica, SHOENFELD, Yehuda
• Format: Article
• Language: English
• Subjects: Aged; Antibodies, Monoclonal - pharmacology; Arteriosclerosis - etiology; Arteriosclerosis - immunology; Arthritis, Rheumatoid - complications; Arthritis, Rheumatoid - diagnostic imaging; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - physiopathology; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular system; Carotid Arteries - diagnostic imaging; Case-Control Studies; CD28 Antigens - blood; CD28 Antigens - drug effects; CD4-Positive T-Lymphocytes - classification; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - physiology; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Humans; Immunophenotyping; Infliximab; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Tumor Necrosis Factor-alpha - immunology; Ultrasonography; Vasodilation - immunology; Vasodilator agents. Cerebral vasodilators
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.0000131450.66017.B3

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. 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. 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.