Migration and activation of T cells during development of graft-versus-host disease in a mouse model

We investigated the pathophysiologic events in graft-versus-host disease (GVHD), a major complication of hematopoietic stem cell transplantation (HSCT).

The experimental group included BALB/c female mice conditioned with 8.0 GY total body irradiation that were transplanted with allogeneic C57BL/6 male bone marrow cells (BMCs) plus CD4(+) T cells and CD8(+) T cells isolated from green fluorescent protein transgenic (eGFP-Tg) C57BL/6 male mice by the immunomagnetic beads negative sorting method. The control group was transplanted only with C57BL/6 male BMCs.

GVHD clinical manifestations were present in the BMCs plus T-cell-transplanted group, but not the BMCs alone group. eGFP(+) T cells were observed in recipient organs, including the liver, spleen, intestine, skin, lungs, tongue, kidneys and even the brain. Donor eGFP(+) T cells were significantly increased in liver and spleen before day +4 (P < .05); but decreased in the spleen while still increased in the liver after day +4 (P < .05). CD25 expression of donor eGFP(+) T cells in the liver and spleen, and interleukin (IL)-2 levels in the peripheral blood was significantly increased before day +4 (P < .05), but decreased after day +4 (P < .05).

These data support the donor T-cell migration hypothesis that accompanied by expression of CD25 and IL-2, during the development of GVHD donor T cells migrate to lymphoid organs, such as the spleen, after activation migrating to GVHD target organs to induce GVHD damage.