登革病毒特异性T细胞在DHF/DSS发病中作用的研究

Dengue virus specific T cells are involved in the pathogenesis of dengue virus infection

目的 研究登革病毒特异性T细胞在登革病毒致病中的作用。方法 首先把培养的HepG2移植到严重联合免疫功能不全 (SCID)小鼠体内 ,建立HepG2 graftedSCID (HepG2 SCID) ,然后将该小鼠分为 3组 :①A组 :登革病毒特异性T细胞 ( 2D42 )接种后次日 ,腹腔内接种 10 6pfu的Ⅱ型登革病毒 (DEN2 ) ;②B组 :正常小鼠胸腺细胞 (NMT)接种后次日 ,腹腔内接种DEN2 ;③C组 :腹腔内接种DEN2。观察感染后各组动物的死亡率、病毒血症及主要脏器的病理变化。结果 接种 2D42细胞 +感染的小鼠 ,80 %出现明显的临床表现 ,并在感染后 12 8d死亡 ,剩余的 2 0 %小鼠有一过性的临床表现 ,然后从疾病中恢复 ,并存活在 3个月以上。而接种NMT +感染或单纯感染的小鼠 ,死亡率均为 10 0 %。A组和B组小鼠血清中的病毒滴度和主要脏器的病理变化发生率明显高于C组。结论 DEN T细胞有保护机体免受病毒侵害和加重病情进展的双重作用 ,而NMT细胞只有加重病情的单一作用。

Objective To study the roles of dengue (DEN) virus specific T cells in the pathogenesis of DEN virus infection. Methods 2D42 cells, DEN virus specific CD8 + cell clones, were employed to investigate their in vivo function in DEN virus infection using an animal model. HepG2 was implanted into mice with severe combined immunodeficiency disease (HepG2-SCID) for the establishment of HepG2-SCID model. The animals were divided into 3 groups: Group A: HepG2-SCID mice were inoculated with 2D42 cells and then infected with DEN virus type 2 (DEN2) intraperitoneally; Group B: HepG2-SCID mice were inoculated with normal mouse thymuscytes (NMT) and then intraperitoneally infected with DEN2; Group C: HepG2-SCID mice were intraperitoneally infected with DEN2 alone. The mortality, viremia, and frequency of histopathological changes in the major organs of mice in the three groups were observed after infection. Results After inoculation of 2D42 cells, 80% infected mice showed severe clinical signs and died at the average 12.8 d after infection. The others only had transient manifestations, and then recovered from the disease and survived for more than 3 months. In contrast, after inoculation of NMT and /or DEN2 alone, 100% mortality rate was noted in these two groups. High viremia and frequency of histopathological changes in the major organs were observed in the mice in groups A and B. Conclusion Our data support both protective and pathogenic roles for DEN-specific CD8 + T cells in DEN virus infection.