Suppression of cell-mediated and humoral immune responses by an interleukin-2-immunoglobulin fusion protein in mice

J Clin Invest. 1996 Mar 1;97(5):1204-10. doi: 10.1172/JCI118534.


Interleukin-2 (IL-2) plays a pivotal role in the cellular and humoral immune responses directed against foreign antigens. We characterized the in vitro and in vivo properties of a chimeric protein consisting of mouse IL-2 fused to the mouse IgG2b Fc domains. This fusion protein binds to IL-2 and Fc receptors and supports IL-2-dependent cell proliferation but does not mediate lysis of IL-2 receptor-positive cells in the presence of murine complement in vitro. However, in vivo the IL2-IgG2b fusion protein suppresses both cellular and humoral immune responses after immunization with sheep erythrocytes. Surprisingly, delayed hypersensitivity is inhibited despite a dramatic increase of splenic CD3+ and NK1.1+ lymphocytes, indicating that altered homing of IL2-IgG2b-activated lymphocytes rather than cytolysis prevents these cells from accumulating in areas of inflammation. Although in vitro the IL2-IgG2b fusion protein does not alter proliferation of B cells in response to mitogenic stimulation, IgM production in response to sheep erythrocytes is profoundly inhibited in mice treated with the IL2-IgG2b fusion protein. Since no side effects are observed, the IL2-IgG2b fusion protein may expand the therapeutic repertoire of reagents used for the treatment of allograft rejection and autoimmune diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation / drug effects
  • Female
  • Hypersensitivity, Delayed
  • Immunoglobulin G / metabolism
  • Immunoglobulin G / pharmacology*
  • Immunosuppressive Agents / pharmacology*
  • Interleukin-2 / metabolism
  • Interleukin-2 / pharmacology*
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Recombinant Fusion Proteins / pharmacology*


  • Immunoglobulin G
  • Immunosuppressive Agents
  • Interleukin-2
  • Recombinant Fusion Proteins