GFC-101

In this study, we demonstrate the influence of human and mouse anti-CD69 therapies on the immune response to VACV infection. We report that targeting CD69 increases the leukocyte numbers in the secondary lymphoid organs during infection and improves the capacity to clear the viral infection. Targeting CD69 increases the numbers of gamma interferon (IFN-γ)- and tumor necrosis factor alpha (TNF-α)-producing NK and T cells. In mice expressing human CD69, treatment with an anti-CD69 MAb produces increases in cytokine production, survival, and proliferation mediated in part by mTOR signaling. These results, together with the fact that we have mainly worked with a human-CD69 transgenic model, reveal CD69 as a treatment target to enhance vaccine protectiveness.

Food allergy prevalence is increasing all over the world. Recent epidemiologic studies have shown the link between vitamin D₃ insufficiency and food allergy occurrence. In this study, we investigated the effect of supplementation with cholecalciferol, a widely used form of vitamin D₃, on food allergy using an experimental mouse model. In wild-type BALB/c mice which were sensitized and challenged with an experimental allergen, ovalbumin, a clinical symptom of food allergy, diarrhea, was significantly induced with the elevation of immunoglobulin E level and the increases of T helper 2 cytokine productions, such as interleukin-4, -5, and -13 (p<0.05), whereas no change in T helper 1 cytokine production, such as interferon-γ, was observed. It was also found that cell population of CD69⁺ CD4⁺ T cells was increased slightly in spleen and significantly in the mesenteric lymphnode with the diarrheal symptom (p<0.05). Treatment of cholecalciferol reduced the allergic diarrhea (p<0.05) with the decreasing tendency of CD69⁺ CD4⁺ T cells, suggesting that the cell population might be associated with the attenuating effect of cholecalciferol on diarrhea occurrence, although immunoglobulin E levels and cytokine productions were not significantly altered by the treatment of cholecalciferol. When given the mice anti-CD69 mAb treatment, significant improvement of allergic diarrhea symptom was observed (p<0.05), accompanying the decrease of CD69⁺ CD4⁺ T cells which suggested the contribution of these cells to the diarrhea symptom. Taken together, we suggest that administration of cholecalciferol might be useful to suppress symptomatic food allergy in association with the decrease of CD69⁺ CD4⁺ T cells.