SummaryAllergen specific CD4+ T cell clones generated from allergic individuals have been shown to produce increased levels of the cytokine interleukin 4 (IL-4), compared to allergen specific clones generated from nonallergic individuals. This difference between CD4+ T cells from allergic and nonallergic individuals with regard to cytokine production in response to allergen is thought to be responsible for the development of allergic disease with increased IgE synthesis in atopic individuals. We examined the production ofIL-4 in subjects with allergic rhinitis and in allergic individuals treated with allergen immunotherapy, a treatment which involves the subcutaneous administration of increasing doses of allergen and which is highly effective and beneficial for individuals with severe allergic rhinitis. We demonstrated that the quantity of IL-4 produced by allergen specific memory CD4+ T cells from allergic individuals could be considerably reduced by in vivo treatment with allergen (allergen immunotherapy) . Immunotherapy reduced IL-4 production by allergen specific CD4+ T cells to levels observed with T cells from nonallergic subjects, or to levels induced with nonallergic antigens such as tetanus toxoid . In most cases the levels of IL-4 produced were inversely related to the length of time on immunotherapy. These observations indicate that immunotherapy accomplishes its clinical effects by reducing IL-4 synthesis in allergen specific CD4+ T cells . In addition, these observations indicate that the cytokine profiles of memory CD4+ T cells can indeed be altered by in vivo therapies . Thus, the cytokine profiles of memory CD4+ T cells are mutable, and are not fixed as had been suggested by studies of murine CD4+ memory T cells. Finally, treatment of allergic diseases with allergen immunotherapy may be a model for other diseases which may require therapies that alter inappropriate cytokine profiles of memory CD4+ T cells .

The aim of this study was to investigate quantitative mRNA expression of matrix metalloproteinases MMP-1, MMP-2, MMP-9, and their inhibitors, the tissue inhibitors of metalloproteinases TIMP-1, TIMP-2 and TIMP-3, in vaginal wall tissue from women with stress urinary incontinence compared to continent controls. Vaginal wall tissues were obtained from 7 women with stress urinary incontinence/severe pelvic prolapse and 15 continent controls. RNA was then extracted and quantified. Quantitative competitive reverse transcription (QC-RT-PCR) was carried out with oligonucleotide primers to quantify MMP-1, MMP-2, MMP-9, TIMP-1, TIMP-2 and TIMP-3 mRNA expression. Stress continent women demonstrated a significant decrease in TIMP-1 and mRNA expression (P = 0.03). There was no difference in TIMP-2, TIMP-3, MMP-2 or MMP-9 mRNA expression between stress incontinent women and controls. However, MMP-1 mRNA expression was significantly increased (P = 0.05) in the incontinent group and the MMP-1/TIMP-1 ratio (P = 0.04) was consistent with increased collagen degradation in the stress incontinence. Stress incontinent women demonstrated an increase in MMP-1 mRNA expression and a decrease in the inhibitor TIMP-1 mRNA expression. Both these findings are consistent with increased collagen breakdown as a pathologic etiology of incontinence.

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Overcoming immune tolerance of the growth factors associated with tumor growth should be a useful approach to cancer therapy by active immunity. We used vascular endothelial growth factor (VEGF) as a model antigen to explore the feasibility of the immunogene tumor therapy with a vaccine based on a single xenogeneic homologous gene, targeting the growth factors associated with angiogenesis. To test this concept, we constructed a plasmid DNA encoding Xenopus homologous VEGF (XVEGF-p) and control vectors. We found that immunogene tumor therapy with a vaccine based on XVEGF was effective at both protective and therapeutic antitumor immunity in several tumor models in mice. VEGF-specific autoantibodies in sera of mice immunized with XVEGF-p could be found in Western blotting analysis and ELISA assay. The purified immunoglobulins were effective at the inhibition of VEGFmediated endothelial cell proliferation in vitro, and at antitumor activity and the inhibition of angiogenesis by adoptive transfer in vivo. The elevation of VEGF in the sera of the tumor-bearing mice could be abrogated with XVEGF-p immunization. The antitumor activity and production of VEGF-specific autoantibodies, significantly elevated IgG1 and IgG2b, could be abrogated by the depletion of CD4 ؉ T lymphocytes. The observations may provide a vaccine strategy for cancer therapy through the induction of autoimmunity against the growth factors associated with tumor growth in a cross reaction with single xenogeneic homologous gene and may be of importance in the further exploration of the applications of other xenogeneic homologous genes identified in human and other animal genome sequence projects in cancer therapy.