Progression from Acute to Chronic Disease in a Murine Parent-into-F_1 Model of Graft-Versus-Host Disease

摘要

The parent-into-immunocometent-F_1 model f graft-vs-host disease (GVIHD),induces immune dysregulation,resulting in acute or chronic GVHD.The disease outcome is thought to be determined by the number of parental anti-F_1 CTL precursor cells present in the inoculum.Injecion of C57BL/6 (B6) splenocytes into (BSXDBA/S)F_1 (B6D2F_1) mice (acute model) leads ot extensive parental cell engraftment and early death,whereas injection fo DBA/2 cells 9chronic model) results in little parental cellengraftment and a lupus-like disease.This study demonstrated that injection of BALB/c splenocytes into (BALB/c X B6)F_1(CB6F_1) mice resulted in little engraftemtn of parental lymphocytes and the development of lupus as expected.injection of B6 splenocytes into CB6F_1 initiated an initial burst of parental cell engraftmentsimilar to that of B6 into B6d2f_1.However,the acute disease resolved,and the CB6F_1 mice went to develop chronic GVHD with detectable Abs to ssDNA,dsDNA,and extractable nuclear Ags.Limting dilution CTL assays detgermiend that B6 splenocytes have CTL precursor frequencies of 1/1000 against both CB6F_1 and B6D2F_1,whereas DBA/2 and BALB/c splenocytes have a CTL precursor frequency of 1/20,000 for their respective F_1s.The Thcell precursor rquency for B6 anti-DBA/2 was 3-fold higher than theat for B6 anti-BALB/c determined by limiting dilution proliferation assays.These results indicate the importance of adequate allospecific heloper as well as effector T cells for the induction and maintenance of acute GVHD in this model,and presents an unexpected model in which initial acute GVHD is replaced by the chronic from of disease.