The T Cells Recognization Of Human Rotavirus And The Development Of Its Diarrhea Model In Miniature Piglets

Group A rotavirus (RV) is the leading cause of severe gastroenteritis in infants and young children around the world. According to recently reports, it is responsible for approximately 138 million episodes of gastroenteritis and 454,000 to 705,000 deaths in the world annually (82% deaths in the developing countries). To date, there is no specific therapy and ideal prophylaxis vaccines licensed for Group A RV. Therefore, it is crucial to get better understanding of the immune protection mechanisms in RV infection.Experiments in mouse models have consistently demonstrated that CD8+T cells could play an important role in protection against RV primary infection and reinfection. Previous study shows that CD8+ T cells from RV-immunized adult mice passively protect suckling mice against RV infection and mediate the clearance of chronic RV infection in SCID mice in the absence of RV-specific antibodies; CD8+T cells-defient mice (β2-microglobulin knockout mice or depletion by anti-CD8 monoclonal antibody) have a 1-4 days delay in clearance of RV infection; B-cell-deficient mice (JHD knockout mice) could mediate the clearance of chronic RV infection and become chronically infected with RV if specific depleted of CD8+ T cells by administration of an anti-CD8 monoclonal antibody. What's more, B-cell-deficient mice could provide completely protection after primary infection 18 days and partial protection after primary infection 6 weeks, 5 months, and 8 months. However, these mice would become chronically infected with RV after rechallenged at 13 day, 18 day, 6 week and 5 month of primary RV infection if specific depleted of CD8+ T cells by administration of an anti- TCRαβ+/+CD8+ T monoclonal antibody, but not by administration of an anti- TCRγδ+/+ monoclonal antibody, which suggestes that it is TCRαβ+/+CD8+ T cells provide protection against RV reinfection. Further studies indicate that VP6 and VP7 protein of RV are main cytotoxicity T lymphocytes (CTL) targets. VP6 is the group antigen of RV, which represents about 51% of the total viral core. The amino acid sequence of the VP6 protein is highly conserved (87 to 99 %) among group A RV.