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Publication : Activated gammadelta T cells promote the activation of uveitogenic T cells and exacerbate EAU development.

First Author  Nian H Year  2011
Journal  Invest Ophthalmol Vis Sci Volume  52
Issue  8 Pages  5920-7
PubMed ID  21296823 Mgi Jnum  J:181442
Mgi Id  MGI:5311315 Doi  10.1167/iovs.10-6758
Citation  Nian H, et al. (2011) Activated gammadelta T cells promote the activation of uveitogenic T cells and exacerbate EAU development. Invest Ophthalmol Vis Sci 52(8):5920-7
abstractText  PURPOSE: To determine how the activation of gammadelta T cells affects the generation of uveitogenic alphabeta T cells and the development of experimental autoimmune uveitis (EAU). METHODS: gammadelta T cells were isolated from B6 mice immunized with the uveitogenic peptide IRBP(1-20) and alphabeta T cells from immunized TCR-delta(-/-) mice. Resting gammadelta T cells were prepared by culture of separated gammadelta T cells in cytokine-free medium for 3 to 5 days, when they showed downregulation of CD69 expression. Activated gammadelta T cells were prepared by incubating resting gammadelta T cells with anti-gammadelta TCR (GL3) for 2 days. Responder alphabeta T cells were cocultured with immunizing antigen and antigen-presenting cells. The numbers of antigen-specific T cells expressing IL-17 or IFN-gamma were determined by intracellular staining followed by FACS analysis after stimulation, with or without the addition of purified gammadelta T cells. The cytokines in the culture medium were measured by ELISA. RESULTS: Highly enriched gammadelta T cells exert widely different effects on autoreactive alphabeta T cells in EAU, depending on the activation status of the gammadelta T cells. Whereas nonactivated gammadelta T cells had little effect on the activation of interphotoreceptor retinoid-binding protein-specific alphabeta T cells in vitro and in vivo, activated gammadelta T cells promoted the generation of uveitogenic T cells and exacerbated the development of EAU. CONCLUSIONS: The functional ability of gammadelta T cells is greatly influenced by their activation status. Activated gammadelta T cells exacerbate EAU through increased activation of uveitogenic T cells.
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