Skip to main content
Identification of a Cytotoxic Form of Dimeric Interleukin-2 in Murine Tissues
  • Lucile E. Wrenshall, Wright State University
  • Suzanne E. Clabaugh, Wright State University - Main Campus
  • David R. Cool, Wright State University - Main Campus
  • Prakash Arumugam, Wright State University - Main Campus
  • William C. Grunwald, Jr., Wright State University - Main Campus
  • Deandra R. Smith
  • Gino C. Liu, Wright State University - Main Campus
  • John D. Miller
Document Type
Publication Date
Interleukin-2 (IL-2) is a multi-faceted cytokine, known for promoting proliferation, survival, and cell death depending on the cell type and state. For example, IL-2 facilitates cell death only in activated T cells when antigen and IL-2 are abundant. The availability of IL-2 clearly impacts this process. Our laboratory recently demonstrated that IL-2 is retained in blood vessels by heparan sulfate, and that biologically active IL-2 is released from vessel tissue by heparanase. We now demonstrate that heparanase digestion also releases a dimeric form of IL-2 that is highly cytotoxic to cells expressing the IL-2 receptor. These cells include “traditional” IL-2 receptor-bearing cells such as lymphocytes, as well as those less well known for IL-2 receptor expression, such as epithelial and smooth muscle cells. The morphologic changes and rapid cell death induced by dimeric IL-2 imply that cell death is mediated by disruption of membrane permeability and subsequent necrosis. These findings suggest that IL-2 has a direct and unexpectedly broad influence on cellular homeostatic mechanisms in both immune and non-immune systems.

© 2014 Wrenshall, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Citation Information
Lucile E. Wrenshall, Suzanne E. Clabaugh, David R. Cool, Prakash Arumugam, et al.. "Identification of a Cytotoxic Form of Dimeric Interleukin-2 in Murine Tissues" PLOS ONE Vol. 9 Iss. 7 (2014) ISSN: 19326203
Available at: