Immune responses induced by T-cell vaccination in patients with rheumatoid arthritis

Abstract

Patients with rheumatoid arthritis (RA) were treated with a cellular vaccine, which consisted of autologous collagen-reactive T-cells. This study showed that antigen-specific proliferative activity of the peripheral blood mononuclear cells was significantly downregulated after T-cell vaccination in RA patients. T-cell vaccination resulted in a statistically significant decrease in plasma IFNγ levels and a concomitant increase in IL-4 levels in treated patients. Accordingly, following T-cell vaccination the number of IFNγ-producing CD4+ and CD8+ T-cells was decreased by 1.6–1.8-fold, which was paralleled by 1.7-fold increases in IL-4-producing CD4+ T-cells. In addition, the present study showed 5–7-fold increase in the CD8+CD45RO+CD62L– effector memory T-cells and central memory T-cells (both CD4+ CD45RO+CD62L+ T-cells and CD8+CD45RO+CD62L+ T-cells) in RA patients, as compared with healthy individuals. We observed significant reduction in CD4+ and CD8+ central memory T-cells, as well as reduction in CD8+ effector memory T-cells in vaccinated patients in the course of the treatment. We also demonstrated that CD4+CD25+FoxP3+ regulatory T-cell levels were significantly up-regulated in the peripheral blood of RA patients following T-cell vaccination. However, CD4+CD25-FoxP3+ Т-cell levels did not significantly change during the entire T-cell vaccination course. In conclusion, the T-cell immunotherapy regimen used resulted in the clinical improvement, which was achieved in 87% patients.

The Impact of T Cell Vaccination in Alleviating and Regulating Systemic Lupus Erythematosus Manifestation

“…No apparent side effects were observed during the treatment and follow-up period, so we assumed attenuated T cell vaccination is safe in use for SLE, which accords with previous studies [15, 17, 18, 34]. …”

“…Attenuated T cells are believed to alleviate manifestation of autoimmune diseases through clearing pathogenic autoreactive T cells [13, 18]. The study supported this idea because antiautoreactive T cell antibodies were observed in W4 and increased in W8, which concurred with the fact that most patients' clinical manifestations were relieved in W4 and were evidently improved in W8, including decreasing SLEDAI and remissions on various clinical features, such as facial rash, low complementemia, and proteinuria.…”

“…The approaches for T cell discretion and expansion were similar to previous studies [15–18]. In brief, peripheral blood mononuclear cells (PBMC) were taken from every patient particularly by Ficoll density gradient centrifugation.…”

Vaccination against autoimmune diseases moves closer to the clinic

“…12 A more recent study on vaccination with collagen II reactive T cells in RA showed a favorable immunological effect with raised levels of activated Foxp-3+ Treg's. 13 Another study with a significant clinical effect of T cell vaccination was carried out with irradiated myelin basic protein (MBP) specific T cells in patients with progressive multiple sclerosis (MS). 14 Along similar lines, my group had carried out some underpinning research on T-T cell interactions the rat model.…”

Immune responses to polyclonal T-cell vaccination in patients with progressive multiple sclerosis

“…We have developed a two-step technology of T-cell vaccine preparation that is technically straightforward, and does not include long-lasting cell culturing procedures making it easily reproducible under the GMP conditions (Ivanova et al 2005(Ivanova et al , 2008(Ivanova et al , 2014. Myelin has been isolated from porcine brain as described previously (Deibler et al 1972).…”