APL1, an altered peptide ligand derived from human heat-shock protein 60, increases the frequency of Tregs and its suppressive capacity against antigen responding effector CD4 + T cells from rheumatoid arthritis patients

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• 作者：Ariana Barberá ; Noraylis Lorenzo ; Peter van Kooten…
• 刊名：Cell Stress and Chaperones
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：21
• 期：4
• 页码：735-744
• 全文大小：1,516 KB
• 刊物主题：Biomedicine general; Cell Biology; Biochemistry, general; Immunology; Cancer Research; Neurosciences;
• 出版者：Springer Netherlands
• ISSN：1466-1268
• 卷排序：21

文摘

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by a chronic relapsing-remitting joint inflammation. Perturbations in the balance between CD4 + T cells producing IL-17 and CD4 + CD25highFoxP3 + Tregs correlate with irreversible bone and cartilage destruction in RA. APL1 is an altered peptide ligand derived from a CD4+ T-cell epitope of human HSP60, an autoantigen expressed in the inflamed synovium, which increases the frequency of CD4 + CD25highFoxP3+ Tregs in peripheral blood mononuclear cells from RA patients. The aim of this study was to evaluate the suppressive capacity of Tregs induced by APL1 on proliferation of effector CD4+ T cells using co-culture experiments. Enhanced Treg-mediated suppression was observed in APL1-treated cultures compared with cells cultured only with media. Subsequent analyses using autologous cross-over experiments showed that the enhanced Treg suppression in APL1-treated cultures could reflect increased suppressive function of Tregs against APL1-responsive T cells. On the other hand, APL1-treatment had a significant effect reducing IL-17 levels produced by effector CD4+ T cells. Hence, this peptide has the ability to increase the frequency of Tregs and their suppressive properties whereas effector T cells produce less IL-17. Thus, we propose that APL1 therapy could help to ameliorate the pathogenic Th17/Treg balance in RA patients.KeywordsRheumatoid arthritisHeat shock protein 60Altered peptide ligandsRegulatory T cells