• Media type: E-Article
  • Title: Interruption in Dendritic Cells Paracrine Delivery of IL-2 to Treg Cells Impairs Their Function. (141.30)
  • Contributor: Nasr, Mohamed E; Kulhankova, Katarina; Rouse, Todd; Field, Elizabeth H
  • imprint: The American Association of Immunologists, 2009
  • Published in: The Journal of Immunology
  • Language: English
  • DOI: 10.4049/jimmunol.182.supp.141.30
  • ISSN: 0022-1767; 1550-6606
  • Keywords: Immunology ; Immunology and Allergy
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title> <jats:p>Regulatory T cell plays an important role in controlling immunity to self and foreign antigens. CD4+CD25+ require T cell receptor and IL-2 receptor activation for in vivo / in vitro expansion and function, but the source of IL-2 remains unknown. In identifying the important paracrine source of IL-2 for Treg cells, we concentrated on the dendritic cell as the paracrine source, because in vitro imaging studies demonstrated fine localization of CD25 at the membrane interface between RD6 and dendritic cells. We used ELISPOT assay to detect IL-2 production by the freshly isolated splenic and bone marrow dendritic cells Dendritic cells secrete a small fraction of IL-2 early in culture, CpG-B enhances the IL-2 production of DCs. Coculture with regulatory cells reduces the level of detectable IL-2.We examined the direct effect of dendritic cell IL-2 on Treg function, CD4+CD25+ cells suppressed CD4+CD25- effectors cells when stimulated with WT dendritic cells, but not when stimulated with IL-2KO DCs. Anti-CD25 abrogates the function of both Treg and RD6 co-cultured with WT DCs, suggesting that CD25 is required for delivery of IL-2 into the Tregs for processing and the addition of high doses of exogenous IL-2 can restore the inhibitory function of Treg and RD6 cells co-cultured with IL-2 -/- dendritic cells. These data suggest that DC IL-2 is essential for Treg function.</jats:p>
  • Access State: Open Access