Delayed allograft rejection in mice transgenic for a soluble form of the IL-4 receptor

Cell Immunol. 1992 Sep;143(2):434-48. doi: 10.1016/0008-8749(92)90038-q.


Accumulating evidence suggests that in serum and other biological fluids, cytokine binding is a property associated with soluble proteins, including a high-affinity soluble version of the IL-4 receptor (sIL-4R). While it is tempting to speculate that sIL-4R might act as a serum carrier protein or serve to inhibit or modulate IL-4 action, specific biological roles for sIL-4R remain to be established. To further assess the immunoregulatory and therapeutic potential of sIL-4R and other soluble receptors, we have created transgenic mice which constitutively express elevated levels of biologically active sIL-4R. Phenotypic characterization of lymphoid organs in sIL-4R transgenic mice revealed normal numbers of B and T cells and normal surface marker expression. Splenic lymphocytes displayed normal in vitro activities as measured by the PFC response and generation of cytotoxic T cells. In addition, antigen-specific IgE and IgG1 in vivo responses were similar in control and transgenic mice. Despite the apparent developmental normality of the sIL-4R transgenic mice, these animals were markedly deficient in the ability to reject cardiac allografts, suggesting that IL-4 is critical for the generation of alloreactivity. The results further suggest that the ability of sIL-4R to regulate IL-4 activities may be under the control of complex interactions that remain to be elucidated.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies / immunology
  • Antibody Formation*
  • Base Sequence
  • Cloning, Molecular
  • Cytotoxicity, Immunologic
  • Graft Rejection*
  • Graft Survival
  • Heart Transplantation / immunology
  • Immunity, Cellular*
  • Immunoglobulin Isotypes / immunology
  • Immunologic Memory
  • Interleukin-4 / physiology*
  • Lymph Nodes / cytology
  • Lymphocyte Activation
  • Mice
  • Mice, Transgenic / immunology*
  • Molecular Sequence Data
  • RNA Splicing
  • Receptors, Interleukin-4
  • Receptors, Mitogen / chemistry
  • Receptors, Mitogen / genetics
  • Receptors, Mitogen / physiology*
  • Solubility
  • Spleen / cytology
  • T-Lymphocytes, Cytotoxic / immunology
  • Trinitrobenzenes / immunology


  • Antibodies
  • Immunoglobulin Isotypes
  • Receptors, Interleukin-4
  • Receptors, Mitogen
  • Trinitrobenzenes
  • Interleukin-4