Vaccination with selected synovial T cells in rheumatoid arthritis
| Autor: | Li Wang, Dongyi He, Ningli Li, Rong Xu, Dongqing Zhang, Baihua Shen, Ying C. Q. Zang, Liqing Ni, Guangjie Chen, Jingwu Zhang, Guozhang Feng |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Adult
Male CD8 Antigens T-Lymphocytes medicine.medical_treatment Immunology Receptors Antigen T-Cell T-cell vaccination Pilot Projects T-Lymphocytes Regulatory Arthritis Rheumatoid Interleukin 21 Immune system Rheumatology medicine Humans Immunology and Allergy Cytotoxic T cell Pharmacology (medical) IL-2 receptor Aged business.industry Synovial Membrane Vaccination Interleukin-2 Receptor alpha Subunit Immunotherapy Active FOXP3 Forkhead Transcription Factors Immunotherapy Middle Aged Gene Expression Regulation CD4 Antigens Female business CD8 |
| Zdroj: | Arthritis & Rheumatism. 56:453-463 |
| ISSN: | 1529-0131 0004-3591 |
| DOI: | 10.1002/art.22316 |
| Popis: | Objective This pilot clinical study was undertaken to investigate the role of T cell vaccination in the induction of regulatory immune responses in patients with rheumatoid arthritis (RA). Methods Autologous synovial T cells were selected for pathologic relevance, rendered inactive by irradiation, and used for vaccination. Fifteen patients received T cell vaccination via 6 subcutaneous inoculations over a period of 12 months. Results T cell vaccination led to induction of CD4+ Tregs and CD8+ cytotoxic T cells specific for T cell vaccine. There was selective expansion of CD4+,Vβ2+ Tregs that produced interleukin-10 (IL-10) and expressed a high level of transcription factor Foxp3, which coincided with depletion of overexpressed BV14+ T cells in treated patients. CD4+ IL-10–secreting Tregs induced by T cell vaccination were found to react specifically with peptides derived from IL-2 receptor α-chain. The expression level of Foxp3 in CD4+ T cells and increased inhibitory activity of CD4+,CD25+ Tregs were significantly elevated following T cell vaccination. The observed regulatory immune responses collectively correlated with clinical improvement in treated patients. In an intent-to-treat analysis, a substantial response, defined as meeting the American College of Rheumatology 50% improvement criteria, was shown in 10 of the 15 patients (66.7%) and was accompanied by a marked improvement in RA-related laboratory parameters. Conclusion These findings suggest that T cell vaccination induces regulatory immune responses that are associated with improved clinical and laboratory variables in RA patients. |
| Databáze: | OpenAIRE |
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