Differential Roles of Granzyme B in GVHD and GVT Effect
Al Qassim, Emad
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Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially effective treatment for many blood cancers . In the HSCT recipients, tumor cells could be attacked by donor-derived immune cells . This immune response has been defined as the graft-versus-tumor (GVT) effect, which is crucial to the effectiveness of allogeneic (HSCT) for cancer patients . However, when donor T cells recognize normal host tissue as foreign and attack them, graft-versus-host disease (GVHD) may develop . The hypothesis is GzmB plays a differential role in CD4+ T cells and Pan- T cells-mediation GVHD and GVT. To test this hypothesis, various strains of mice were used as donors and recipients. To generate GVHD model, mice were irradiated, and on day later were injected intravenously with TCD-BM cells only CD4+ CD25- T cells isolated from donor WT or GzmB-/- mice. The hosts were weighed twice every week and monitored for survival. GVT model was generated like GVHD model but the host mice were inoculated through lateral tail vein with luciferase-expressing cells. Bioluminescence imaging was performed to monitor tumor burden. The results showed that GzmB diminished the ability of CD4+ CD25- T cells to cause lethal GVHD, while in the same time it contributes to the optimal GVT activity of CD4+ CD25- T cells. Pan-T cells (CD4+ T cell + CD8+ T cell) exhibit roles in GVHD and GVT depend on dose of donor T cells but GzmB has no role in this effect. These results confirmed that GzmB has a role in mice received CD4+ CD25- T cells but not in mice received Pan-T cells. This confirms the opposite role of GzmB in CD4 and CD8+ T-cells.