Delayed allograft rejection in mice transgenic for a soluble form of the IL-4 receptor.
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.
Maliszewski
C R
CR
Department of Immunology, Immunex Research & Development Corporation, Seattle, Washington 98101.
Morrissey
P J
PJ
Fanslow
W C
WC
Sato
T A
TA
Willis
C
C
Davison
B
B
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation; D001483:Base Sequence; D003001:Cloning, Molecular; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology; D007111:Immunity, Cellular; D007132:Immunoglobulin Isotypes / Q000276:immunology; D007156:Immunologic Memory; D015847:Interleukin-4 / Q000502:physiology*; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic / Q000276:immunology*; D008969:Molecular Sequence Data; D012326:RNA Splicing; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D012995:Solubility; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014301:Trinitrobenzenes / Q000276:immunology
D000906:Antibodies; D007132:Immunoglobulin Isotypes; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D014301:Trinitrobenzenes; D015847:Interleukin-4