Long term expression of IL-4 in vivo using retroviral-mediated gene transfer.
Th cell subsets regulate immune responses by cell-cell interaction and secretion of cytokines. IL-4 is one of the cytokines secreted by Th cells important for cellular and humoral, particularly IgG1 and IgE responses. To study the role of IL-4 in T cell development and regulation of immune responses in vivo, low IgE-responder C57BL/6 mice were reconstituted with bone marrow cells that had been infected with recombinant retrovirus expressing a high level of IL-4. The reconstituted mice expressed retroviral IL-4 transcripts (9/10) even 8 mo postreconstitution. Physiologically significant levels of IL-4 were detected in the majority of the provirus-positive animals tested (5/8). Ectopic expression of exogenous IL-4 in hematopoietic cells had dramatic effects on T cell development resulting in changes in CD4:CD8 ratios. Moreover, the levels of serum IgG1 and, with antigenic stimulation, IgE were also increased. These results demonstrate that the retrovirus gene transfer system can be used to study the effects of ectopic cytokine gene expression in vivo on Ig isotype regulation and T helper cell subset differentiation.
Chambers
C A
CA
Division of Molecular Immunology and Neurobiology, Mount Sinai Hospital, Toronto, Ontario, Canada.
Kang
J
J
Hozumi
N
N
D000818:Animals; D000917:Antibody Formation; D001483:Base Sequence; D005434:Flow Cytometry; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis*; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012190:Retroviridae / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection
D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; D015847:Interleukin-4; D007073:Immunoglobulin E