Th1-dominant shift of T cell cytokine production, and subsequent reduction of serum immunoglobulin E response by administration in vivo of plasmid expressing Txk/Rlk, a member of Tec family tyrosine kinases, in a mouse model.
BACKGROUND
Th1 and Th2 cells, resulting from antigenic stimulation in the presence of IL-12 and IL-4, respectively, are implicated in the pathology of various diseases including allergic and autoimmune diseases. Txk/Rlk is a member of Tec family tyrosine kinases. We reported that Txk acts as a Th1-specific transcription factor in the T lymphocytes.


OBJECTIVE
In this study we have asked whether administration of txk expression plasmid brings about a Th1/Th2 shift in vivo of the mice, and subsequent reduction of circulating IgE.


METHODS
Mice were administered a txk expression plasmid with hemagglutinating virus of Japan (HVJ) envelope vector. Txk expressions in spleen cells were assessed by immunoblotting and immunocytochemical staining. Cytokine productions by the spleen cells and serum Ig concentrations were studied by ELISA.


RESULTS
Administration of a txk expression plasmid with HVJ vector induced expression of Txk in the spleen cells. The spleen cells showed enhanced Th1-specific cytokine production; spleen cells from the txk administered mice produced more IFN-gamma as compared with those from control plasmid-administered mice in an antigen-specific manner. IL-2 and IL-4 secretions of the spleen cells were comparable between the two mouse groups. Txk administration did not reduce serum IgG concentration. It markedly reduced total IgE level and an IgG1/IgG2a ratio, reflection of Th1/Th2 balance, in sera. Furthermore, txk administration reduced ovalbumin (OVA)-specific IgE levels in sera of the OVA sensitized mice.


CONCLUSIONS
Thus, Txk enhances IFN-gamma secretion and thus modulates Th1/Th2 cytokine balance, leading to reduction of serum IgE.
Takeno
M
M
Department of Immunology, St Marianna University School of Medicine, Kawasaki, Japan.
Yoshikawa
H
H
Kurokawa
M
M
Takeba
Y
Y
Kashiwakura
J-I
JI
Sakaguchi
M
M
Yasueda
H
H
Suzuki
N
N
D000818:Animals; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage; D007073:Immunoglobulin E / Q000097:blood*; D007150:Immunohistochemistry / Q000379:methods; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D029082:Sendai virus / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology*; D014161:Transduction, Genetic / Q000379:methods*
D007073:Immunoglobulin E; D007371:Interferon-gamma; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases