期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 17, 期 4, 页码 1075-1083出版社
ELSEVIER
DOI: 10.1016/j.intimp.2013.10.010
关键词
Rheumatoid arthritis; Heat shock protein 60; Altered peptide ligands; Epitope-specific immunotherapy
资金
- Women in Science Program
- L'Oreal/UNESCO
- Dutch Arthritis Foundation and the Innovation Oriented Programme Genomics
Rheumatoid arthritis (RA) is a chronic T-cell mediated autoimmune disease that affects primarily the joints. The induction of immune tolerance through antigen-specific therapies for the blockade of pathogenic CD4 + T cells constitutes a current focus of research. In this focus it is attempted to simultaneously activate multiple regulatory mechanisms, such as: apoptosis and regulatory T cells (Tregs). APL-1 is an altered peptide ligand derived from a novel CD4+ 1-cell epitope of human heat-shock protein of 60 kDa, an autoantigen involved in the pathogenesis of RA Previously, we have reported that APL-1 induces CD4+ CD25thghFoxp3 + Tregs in several systems. Here, we investigated the ability of APL-1 in inducing apoptosis in PBMCs from RA patients, who were classified as active or inactive according to their DAS28 score. APL-1 decreased the viability of PBMCs from active but not from inactive patients. DNA fragmentation assays and typical morphological features clearly demonstrated that APL-1 induced apoptosis in these cells. Activated CD4 + CD25 + T cells but not resting CD4 + CD25 T cells were identified as targets of APL-1. Furthermore, CD4 + 1-cell responses to APL-1 were found to be dependent on antigen presentation via the HLA-DR molecule. Thus, APL-1 is a regulatory CD4 + T cell epitope which might modulate inflammatory immune responses in PBMCs from RA patients by inducing CD4+ CD25highFoxp3 + Tregs and apoptosis in activated CD4+ T cells. These results support further investigation of this candidate drug for the treatment of RA (C) 2013 Elsevier B.V. All rights reserved.
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