关键词: 骨髓移植, CD8⁺+T细胞, 移植物抗宿主病(GVHD)

Abstract: Objective To study the relationship between memory CD8⁺ T cell and GVHD by using a mouse model of CD8^??+ T cell-mediated acute graft versus host disease(GVHD). Methods C3H. SW(H-2D^b, CD45.2^?+) mice were used as donors and B6/SJL(H-2D^b, CD45.1⁺) mice as recipients, both of them are MHC-identical but miHA-mismatched. Before transplantation, the B6 recipients received ^{137y ray}(9.5 Gy) TBI administered in three times from a ¹³⁷Cs source, then the T cell-depleted bone marrow (T" BM) cells and CD8⁺Tcells from C3H.SW donors were injected immediately via tail vein. The weights of recipient mice and dead rate were calculated after transplantation. Results The quantitative changes in the livers and spleens of recipient mice of the donor CD8⁺T cells(CD45.2^?+), donor CD8⁺T cells that produced IFN-Y and the apoptosis related molecular annexin V on donor CD8⁺T cells were analyzed by Flow Cytometry. In the miHA-mismatched CD8+ T cell-mediated acute GVHD mouse model, the recipient mice began to die 28 days following transplantation and the dead rate was 58% until 70 days. The analysis showed that in parallel to GVHD development, donor CD8⁺T cells and CD8⁺T cells secreting high levels of IFN-Y peaked in the livers and spleens of recipient mice by day 14，considerably declined by day 28, increased again by day 42 after transplantation. The decline in donor CD8⁺T cells was accompanied with increased annexin V-positive donor CD8⁺T cells. These results suggest that a typical memory T cell response，as manifested by T cell expansion, contraction, and re-expansion, develops in recipients during the GVHD process，and a small population of reactive CD8⁺T cells survives after the death phase of effect cells. Conclusions The MHC-identical but miHA mismatched mouse model is analogous to human clinical miHA-mismatched bone marrow transplantation. There is the relation of the donor CD8⁺ T cells to GVHD persistence.

Key words: Marrow transplantation, CD8T cell, Graft-vers us-host disease