Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Interleukin-27 promotes CD8+ T cell reconstitution following antibody-mediated lymphoablation
Katayoun Ayasoufi, … , Robert L. Fairchild, Anna Valujskikh
Katayoun Ayasoufi, … , Robert L. Fairchild, Anna Valujskikh
Published April 4, 2019
Citation Information: JCI Insight. 2019;4(7):e125489. https://doi.org/10.1172/jci.insight.125489.
View: Text | PDF
Research Article Immunology Transplantation

Interleukin-27 promotes CD8+ T cell reconstitution following antibody-mediated lymphoablation

  • Text
  • PDF
Abstract

Antibody-mediated lymphoablation is used in solid organ and stem cell transplantation and autoimmunity. Using murine anti-thymocyte globulin (mATG) in a mouse model of heart transplantation, we previously reported that the homeostatic recovery of CD8+ T cells requires help from depletion-resistant memory CD4+ T cells delivered through CD40-expressing B cells. This study investigated the mechanisms by which B cells mediate CD8+ T cell proliferation in lymphopenic hosts. While CD8+ T cell recovery required MHC class I expression in the host, the reconstitution occurred independently of MHC class I, MHC class II, or CD80/CD86 expression on B cells. mATG lymphoablation upregulated the B cell expression of several cytokine genes, including IL-15 and IL-27, in a CD4-dependent manner. Neither treatment with anti-CD122 mAb nor the use of IL-15Rα–/– recipients altered CD8+ T cell recovery after mATG treatment, indicating that IL-15 may be dispensable for T cell proliferation in our model. Instead, IL-27 neutralization or the use of IL-27Rα–/– CD8+ T cells inhibited CD8+ T cell proliferation and altered the phenotype and cytokine profile of reconstituted CD8+ T cells. Our findings uncover what we believe is a novel role of IL-27 in lymphopenia-induced CD8+ T cell proliferation and suggest that targeting B cell–derived cytokines may increase the efficacy of lymphoablation and improve transplant outcomes.

Authors

Katayoun Ayasoufi, Daniel B. Zwick, Ran Fan, Suheyla Hasgur, Michael Nicosia, Victoria Gorbacheva, Karen S. Keslar, Booki Min, Robert L. Fairchild, Anna Valujskikh

×

Figure 8

IL-27R expression is required for optimal CD8+ T cell reconstitution.

Options: View larger image (or click on image) Download as PowerPoint
IL-27R expression is required for optimal CD8+ T cell reconstitution.
Sp...
Splenic CD8+ T cells were isolated from B6.CD45.1+ WT and B6.IL-27Rα–/– CD45.2+ mice and coinjected into B6.CD45.1/2+ mice followed by BALB/c heart transplantation and mATG treatment. The control group of B6.CD45.1/2+ recipients was injected with CD8+ T cells but did not receive heart transplant or mATG treatment. (A) Representative dot plots analyzing transferred WT and IL-27Rα–/– CD8+ T cells in peripheral blood at indicated time points. Data are shown after gating on CD8+ cells. (B) The percentages of total and transferred CD8+ T cells in peripheral blood. The results are representative of 4 independent experiments with n = 4 mice/group; error bars represent SD. P values were determined by 2-tailed Student’s t test.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts