Antigen-presenting effects of effector memory Vγ9Vδ2 T cells in rheumatoid arthritis

Rheumatoid arthritis is an autoimmune disease that primarily affects the limbs, but the pathogenic mechanism remains unclear. gamma delta 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 gamma delta T cells and their relationship with rheumatoid arthritis development. We found that V gamma 9V delta 2 T cells ( the predominant subtype of gamma delta T cells in peripheral blood) were activated by isopentenyl pyrophosphate to continuously proliferate and differentiate into effector memory cells. The effector memory Vc gamma V delta 2 T cells exhibited phenotypic characteristics of specific antigen-presenting cells, including high HLA-DR and CD80/86 expression. These Vc gamma V delta 2 T cells could present soluble antigens and synthetic peptides to CD4(+) T cells. V gamma 9V delta 2 T cells with different phenotypes showed different cytokine secretion patterns. Effector memory V gamma 9V delta 2 T cells simultaneously secreted not only interferon (IFN)-gamma but also IL-17. The peripheral blood and joint synovial fluid from RA patients contained numerous heterogeneous gamma delta T cells that were predominantly effector memory V gamma 9V delta 2 T cells with the ability to secrete inflammatory factors. We also found that gamma delta T cells had a similar antigen-presenting capability to B cells. These results suggest that during the development of rheumatoid arthritis, gamma delta 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, gamma delta 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. Cellular & Molecular Immunology (2012) 9, 245-254; doi:10.1038/cmi.2011.50; published online 5 December 2011