Induction of antiidiotypic immune response with autologous T-cell vaccine in patients with multiple sclerosis

Abstract

Patients with different forms of multiple sclerosis were treated with a vaccine consisting of myelin-reactive T cells. It was found that after this treatment, lymphocytes from patients acquired the capacity to generate antiidiotypic proliferative response directed towards myelin-reactive T cells. The serum concentration of IFN-gamma decreased about 2-fold 1.5-2.0 years after the start of vaccine therapy, whereas the concentration of IL-4 increased 2-3 fold. Myelin-reactive proliferative activity of peripheral blood mononuclear cells also decreased. The results of the 2-year follow-up study revealed no side effect of T-cell vaccination in patients with cerebrospinal form of multiple sclerosis and demonstrated its possible clinical efficiency in the treatment of this disease at early stages.

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).…”

“…Step 2 consisted in the expansion of antigen-specific cells in the presence of 5 lg PHA/ml (phytohemagglutinin, Sigma) and recombinant IL-2 (100 U/ml, Biotech, St. Petersburg, Russia) for 5 d. T-Cells expanded in this manner have been previously shown to maintain increased reactivity to myelin antigens (Ivanova et al 2008). The total cell number obtained from one patient ranged between 18 and 27 Â 10 7 .…”

“…PBMC isolated from vaccinated MS patients demonstrated an increase in proliferative activity in the presence of vaccinal myelin-reactive, but not collagen-reactive T-cells. Anti-idiotypic T-cell lines raised from TCVtreated MS patients produced IL-4 and IL-10 in response to specific activation (Ivanova et al 2008).…”

“…Such vaccines were found to be safe for clinical use and effective in inducing anti-idiotypic immune responses in MS patients. Considerable immune and clinical efficacy was noted in certain patients with relapsing MS (Ivanova et al 2005(Ivanova et al , 2008. The aim of this study was to evaluate safety and immune efficacy of a polyclonal T-cell vaccination in patients with chronic MS in advanced stages of the disease when disease management is most problematic.…”

Regulatory T cells play a role in T‐cell receptor CDR2 peptide regulation of experimental autoimmune encephalomyelitis

“…1,2 For reasons that are unclear, organ-specific autoreactive T cells become activated and expand in some individuals to the point of causing severe tissue destruction. A therapeutic strategy for controlling such autoreactive processes has been the use of the pathogenic T cells themselves, [3][4][5][6][7][8][9][10] or receptors from these T cells, as a vaccine to potentiate a natural immunoregulatory function against the pathogenic T cells. T-cell receptor (TCR) protein [11][12][13] and TCR peptide therapy [14][15][16][17] have been shown to be effective at suppressing autoimmunity in several rodent models, as well as in human clinical trials.…”