EFFICACY OF GCV FOR EXPERIMENTAL ACUTE GRAFT VERSUS HOST DISEASE REPLICATED BY INFUSION OF H-2 HAPLOTYPE MATCHED CD34~+ CELLS IN COMBINATION WITH TK~+T LYMPHOCYTES TRANSPLANTATION / 解放军医学杂志

ABSTRACT

Objective To study the therapeutic efficacy of HSV-TK/GCV in acute graft versus host disease (GVHD) produced by infusion of H-2 haplotype matched CD34 + cells in combination with TK +T lymphocytes transplantation. Methods CD34 + cells were separated from bone marrow of male donor mice, and T lymphocytes were acquired from the spleen and transfected with retroviral vectors carrying tk gene. Forty-eight female F1 recipient mice were divided into six groups. Group 1 received 1?10 5 CD34 + cells, groups 2 and 3 received 1?10 5 CD34 + cells and 1?10 7 T lymphocytes, groups 4～6 received 1?10 5 CD34 + cells and 1?10 7 TK +T lymphocytes. GCV was administered to group 5 and group 6 in the dosage of 50mg/(kg?d) for 7 days by intraperitoneal injection on day 0 and 7 posttransplant, respectively. Results All the recipient mice in group 1 survived more than 30 days and no acute GVHD symptoms emerged. Acute GVHD symptoms appeared in the recipient mice in groups 2～6 showing typical pathological manifestations. The recipient mice in groups 2～4 died of acute GVHD 3 weeks posttransplant. The survival time of recipient mice in groups 5 and 6 was 26.6?4.8 days and 40.5?8.4 days, respectively, which was significantly longer than that of groups 2～4 (P