Dengue-specific CD8+ T cells have both protective and pathogenic roles in dengue virus infection

Abstract

To analyze roles of memory T cells in the pathogenesis of dengue (DEN) virus infection, a DEN virus-specific CD8+ cell clone (2D42 cell) was employed to investigate its in vivo function after DEN virus infection using an animal model. HepG2 grafted severe combined immunodeficient (HepG2-grafted SCID) mice were divided into three groups--group A: HepG2-grafted SCID mice were inoculated intraperitoneally (ip) with 2D42 cells and then ip-infected with DEN virus type 2 (DEN-2); group B: HepG2-grafted SCID mice were inoculated with naive mouse thymocytes (NMT) and then ip-infected with DEN-2; group C: HepG2-grafted SCID mice were ip-infected with DEN-2 alone. Eighty percentage of group A mice died at average day 12.8 post-infection (p.i.) and 20% of them recovered from the disease after showing clinical signs and survived more than 3 months. They showed severe manifestations including dramatically decreased platelet count, decreased hematocrit, anemia, viremia and high frequency of histopathological changes in several organs. All of group B mice also showed the above severe clinical signs. One hundred percentage mortality rate was noted in these mice and death occurred at average day 10.8 p.i., which was the earliest among three groups. Although the mice from group C showed 100% mortality rate and similar clinical signs, death observed in these mice occurred at average day 17.4 p.i. and the manifestations were slight and developed slowly. Our results suggested both protective and pathogenic roles for DEN-specific CD8+ T cell in DEN virus infection, whereas NMT did not provided any protection.