Praziquantel Facilitates IFN-γ-Producing CD8+ T Cells (Tc1) and IL-17-Producing CD8+ T Cells (Tc17) Responses to DNA Vaccination in Mice

BACKGROUND: CD8(+) cytotoxic T lymphocytes (CTLs) are crucial for eliminating hepatitis B virus (HBV) infected cells. DNA vaccination, a novel therapeutic strategy for chronic virus infection, has been shown to induce CTL responses. However, accumulated data have shown that CTLs could not be effectively induced by HBV DNA vaccination. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that praziquantel (PZQ), an anti-schistoma drug, could act as an adjuvant to overcome the lack of potent CTL responses by HBV DNA vaccination in mice. PZQ in combination with HBV DNA vaccination augmented the induction of CD8(+) T cell-dependent and HBV-specific delayed hypersensitivity responses (DTH) in C57BL/6 mice. Furthermore, the induced CD8(+) T cells consisted of both Tc1 and Tc17 subtypes. By using IFN-γ knockout (KO) mice and IL-17 KO mice, both cytokines were found to be involved in the DTH. The relevance of these findings to HBV immunization was established in HBsAg transgenic mice, in which PZQ also augmented the induction of HBV-specific Tc1 and Tc17 cells and resulted in reduction of HBsAg positive hepatocytes. Adoptive transfer experiments further showed that PZQ-primed CD8(+) T cells from wild type mice, but not the counterpart from IFN-γ KO or IL-17 KO mice, resulted in elimination of HBsAg positive hepatocytes. CONCLUSIONS/SIGNIFICANCE: Our results suggest that PZQ is an effective adjuvant to facilitate Tc1 and Tc17 responses to HBV DNA vaccination, inducing broad CD8(+) T cell-based immunotherapy that breaks tolerance to HBsAg

Girl\u27s Softball in Richmond, Kentucky

From the sport’s creation in 1876, women’s fastpitch softball is a sport that has evolved nationally and worldwide. The organization of travel fastpitch softball teams, with participants ranging from 8 to 18 years old, has encouraged and increased the competitiveness of the game. Travel teams saw tremendous growth in the early 2000s. Nationwide tournaments that host the most talented teams attract hundreds of collegiate coaches to scout potential future players in hopes of offering them the ultimate goal: a college scholarship. While many cities and states are well advanced in the sport, there are some cities that struggle to grow. Richmond, Kentucky is a location where girl’s softball is present, however, the sport is struggling to expand. Factors that affect the growth and advancement of girl’s softball in Richmond include, funding, quality and amount of adequate facilities, the absence of experienced coaches and loss of interest. The research question to be examined is how do we improve these factors so that girl’s softball in Richmond can grow? This study involved a literature review as well as interviews with players, coaches, and parks and recreation professionals to ascertain the issues facing girls’ softball in Richmond, Kentucky