Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes
David H. Munn, … , Pandelakis A. Koni, Andrew L. Mellor
David H. Munn, … , Pandelakis A. Koni, Andrew L. Mellor
Published July 15, 2004
Citation Information: J Clin Invest. 2004;114(2):280-290. https://doi.org/10.1172/JCI21583.
View: Text | PDF | Erratum
Article Oncology

Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes

  • Text
  • PDF
Abstract

One mechanism contributing to immunologic unresponsiveness toward tumors may be presentation of tumor antigens by tolerogenic host APCs. We show that mouse tumor-draining LNs (TDLNs) contained a subset of plasmacytoid DCs (pDCs) that constitutively expressed immunosuppressive levels of the enzyme indoleamine 2,3-dioxygenase (IDO). Despite comprising only 0.5% of LN cells, these pDCs in vitro potently suppressed T cell responses to antigens presented by the pDCs themselves and also, in a dominant fashion, suppressed T cell responses to third-party antigens presented by nonsuppressive APCs. Adoptive transfer of DCs from TDLNs into naive hosts created profound local T cell anergy, specifically toward antigens expressed by the transferred DCs. Anergy was prevented by targeted disruption of the IDO gene in the DCs or by administration of the IDO inhibitor drug 1-methyl-D-tryptophan to recipient mice. Within the population of pDCs, the majority of the functional IDO-mediated suppressor activity segregated with a novel subset of pDCs coexpressing the B-lineage marker CD19. We hypothesize that IDO-mediated suppression by pDCs in TDLNs creates a local microenvironment that is potently suppressive of host antitumor T cell responses.

Authors

David H. Munn, Madhav D. Sharma, Deyan Hou, Babak Baban, Jeffrey R. Lee, Scott J. Antonia, Jane L. Messina, Phillip Chandler, Pandelakis A. Koni, Andrew L. Mellor

×

Figure 3

Options: View larger image (or click on image) Download as PowerPoint
Dominant third-party suppression mediated by IDO+ pDCs. Two independent ...
Dominant third-party suppression mediated by IDO+ pDCs. Two independent pairs of APCs and responder T cells were used to test the effect of IDO on third-party T cell responses. IDO+ pDCs from TDLNs presented H2Kb antigen to BM3 T cells, while IDO– DCs (sorted CD11c+ cells from normal CBA spleen) presented antigen to TCR-transgenic CD4+ T cells (recognizing a peptide from HY, restricted on H2Ek). In both cases, the APC/T cell ratio was 1:25. Graded numbers of the pDC+BM3 pair were added to 1 × 105 cells of the DC+αHY pair, and the total proliferation was measured after 72 hours. The number of IDO+ pDCs added is shown on the x axis (with 4,000 cells reflecting a 1:1 ratio between the two pairs of MLRs). Duplicate sets of wells received either 1MT (squares) or no 1MT (triangles).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts