Synergistic enhancement of T cell responses and interleukin-1 receptor expression by interleukin-1 and heparin or dextran sulfate.
Heparin markedly enhances generation of cytotoxic T lymphocytes against allogeneic cells and histocompatible tumors. In this study, we demonstrated a marked synergism between heparin and low concentrations of recombinant IL-1-alpha and IL-1-beta in enhancement of cytotoxic T cell responses in mice. Low molecular weight (8000 Da) dextran sulfate also enhanced the T cell responses and synergized with IL-1, whereas, de-N-sulfated heparin was devoid of both of these activities. The synergistic effect was selective for IL-1, because there was no synergism between heparin or dextran sulfate and other cytokines (tumor necrosis factor-alpha, IL-4, and, as shown previously, IL-2). Heparin did not increase the production of IL-1 (and IL-2, as shown before). Heparin did not bind to IL-1, despite significant amino acid homology between IL-1 and heparin-binding endothelial cell growth factors. Heparin enhanced the growth-promoting effect of IL-1 on the IL-1-dependent helper T cell clone, D10.G4.1, and enhanced IL-1 receptor expression on these cells. These data indicate that heparin acts directly on the T cells and enhances their responsiveness to IL-1 by up-regulating IL-1 receptor expression.
Dziarski
R
R
Northwest Center for Medical Education, Indiana University School of Medicine, Gary 46408.
D000818:Animals; D002460:Cell Line; D016264:Dextran Sulfate / Q000494:pharmacology*; D004357:Drug Synergism; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D017472:Receptors, Interleukin-1 / Q000032:analysis / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D006493:Heparin; D016264:Dextran Sulfate