Abstract
Rheumatoid arthritis is an autoimmune disease that primarily affects the limbs, but the pathogenic mechanism remains unclear. γδ T cells, a T-cell subpopulation, are characterized by multiple biological functions and associated with a variety of diseases. This study investigated the antigen-presenting effects of γδ T cells and their relationship with rheumatoid arthritis development. We found that Vγ9Vδ2 T cells (the predominant subtype of γδ T cells in peripheral blood) were activated by isopentenyl pyrophosphate to continuously proliferate and differentiate into effector memory cells. The effector memory Vγ9Vδ2 T cells exhibited phenotypic characteristics of specific antigen-presenting cells, including high HLA-DR and CD80/86 expression. These Vγ9Vδ2 T cells could present soluble antigens and synthetic peptides to CD4+ T cells. Vγ9Vδ2 T cells with different phenotypes showed different cytokine secretion patterns. Effector memory Vγ9Vδ2 T cells simultaneously secreted not only interferon (IFN)-γ but also IL-17. The peripheral blood and joint synovial fluid from RA patients contained numerous heterogeneous γδ T cells that were predominantly effector memory Vγ9Vδ2 T cells with the ability to secrete inflammatory factors. We also found that γδ T cells had a similar antigen-presenting capability to B cells. These results suggest that during the development of rheumatoid arthritis, γδ T cells can aggravate immune dysfunction and produce abnormal immune damage by secreting cytokines and inducing inflammatory cells to participate in synergistic inflammatory responses. Furthermore, γδ T cells can behave similarly to B cells to present viral peptides and autoantigen peptides to CD4+ T cells, thus sustaining CD4+ T-cell activation.
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Acknowledgements
This work was supported by the grants from the following: National Natural Science Foundation of China (no. 30471593, 30872304 and 81072470), Shanghai Commission of Science and Technology (no. 10JC14 08500 and 10ZR1426100), Shanghai Leading Academic Discipline-Surgery (no. S30204-K01), Shanghai Municipal education Commission (no. J50207 and 09YZ102), Shanghai Institute of Immunology (no. 08-A04), Clinical Medicine Technology Development Foundation of Jiangsu University (no. JLY2010091) and Foundation of Shanghai Xuhui Central Hospital (no. 2011XHCH07).
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Hu, C., Qian, L., Miao, Y. et al. Antigen-presenting effects of effector memory Vγ9Vδ2 T cells in rheumatoid arthritis. Cell Mol Immunol 9, 245–254 (2012). https://doi.org/10.1038/cmi.2011.50
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DOI: https://doi.org/10.1038/cmi.2011.50
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