Increased expression of interleukin-18 receptor on T lymphocytes in patients with acute graft-versus-host disease after allogeneic bone marrow transplantation

Acute graft-versus-host disease (aGVHD), a potentially fatal side effect of allogeneic bone marrow transplantation (BMT), is initiated by the action of donor-derived T lymphocytes. We have shown previously that aGVHD is associated with elevated serum levels of interleukin-18 (IL-18). In this study, we analyzed the expression of the IL-18 receptor (IL-18R) on T lymphocytes of BMT patients with aGVHD. Flow cytometric analysis showed that in healthy subjects, a small population of CD4(+) T cells expressed IL-18Ralpha, whereas a relatively large population of CD8(+) T cells expressed IL-18Ra. In aGVHD patients, there were marked increases in the proportion of CD4(+) or CD8(+) T cells that express IL-18Ra. RT-PCR assays showed elevation of IL-18Ralpha and IL-18Rbeta mRNA levels in CD8(+) T cells in aGVHD patients. These findings suggest that the expression of IL-18R is upregulated in T cells in patients with aGVHD and that the IL-18/IL-18R system is active during aGVHD.