Therapy with infliximab decreases the CD4+CD28? T cell compartment in peripheral blood in patients with rheumatoid arthritis

Abstract

Chronic inflammatory syndromes such as rheumatoid arthritis (RA) are associated with high frequencies of CD4+CD28- T cells. The number of these cells is genetically determined and may also be a consequence of chronic exposure to tumor necrosis factor-alpha (TNFalpha). The aim of this study was to examine whether the reported efficacy of anti-TNFalpha therapy in RA involves a resurgence of T cell populations that re-express CD28. After 36-week therapy with infliximab, a significant decrease in CD4+CD28- T cells in RA patients was observed in comparison with baseline. The results suggest that TNFalpha-neutralizing therapy may restore T cell homeostasis and reduce expansion of the CD28- T cells, which are cytotoxic and may contribute to organ manifestations in RA.

Modulation of CD4 + CD28 null T Lymphocytes by Tumor Necrosis Factor-α Blockade in Patients With Unstable Angina

“…The CD4 ϩ CD28 null T-cell reduction observed in this study (33%) is similar to that reported in the study by Gerli et al, 21 which showed a 34% reduction in CD4 ϩ CD28 null T cells in patients with rheumatoid arthritis treated with infliximab. In the study by Pawlik et al, 22 a 36% reduction in CD4 ϩ CD28 null T cells was observed after treatment with infliximab. Because TNF-␣ downregulates the expression of CD28 on T cells at the transcriptional level, inhibition of TNF-␣ is likely to restore the presence of CD28 on cell surface by preventing TNF-␣-mediated downregulation of CD28 production.…”

“…On the basis of previous studies in patients with UA and in patients with rheumatoid arthritis, 17,19,21,22 we assumed that the percentage of CD4 ϩ CD28 null T cells likely to be found in our population was 10% (range, 5% to 14%). Moreover, in line with the findings reported by Gerli et al, 21 we assumed that a 34% reduction in CD4 ϩ CD28 null T cells after treatment with infliximab would have been significant.…”

“…22 Pawlik et al 22 have demonstrated that in patients with rheumatoid arthritis, treatment with infliximab achieved a 36% decrease in CD4 ϩ CD28 null T cells together, with an improvement in symptoms and functional capacity. Interestingly, the degree of CD4 ϩ CD28 null T-cell reduction observed by Pawlik et al is similar to that observed in our study, suggesting that our findings may be clinically relevant in patients with UA.…”

Severe Refractory Hidradenitis Suppurativa in an HIV-Positive Patient Successfully Treated With Infliximab

“…[2][3][4]13 Conflicting data can be found on the association between infliximab treatment and its potential effect on CD4 ϩ lymphocyte cell count. 14,15 Ferjolj et al 14 found a significant increase in the concentration of CD3 ϩ , CD4 ϩ , and CD8 ϩ T lymphocytes after infliximab treatment. However, a decrease of the CD4 ϩ CD28 − T-cell compartment in peripheral blood after infliximab therapy in patients with rheumatoid arthritis was reported.…”

Kardiovaskuläre Manifestationen bei Rheumatoider Arthritis

“…Eine therapeutische Blockade von TNFa führt zur Verbesserung der Vasomotorik [23]. Offen bleibt, inwieweit die unter TNFa-Blockade erfolgende Reduktion des Anteils klonal expandierter autoreaktiver T-Zellen für diese Beobachtung verantwortlich ist [63].…”