Transplantation-Related Complications Predicted by Cytokine Gene Expression in the Mixed Lymphocyte Culture in Allogeneic Bone Marrow Transplants

Abstract

In this study, we have investigated cytokine (IL-1β, IL-2, IL-5, IL-6, IFN-γ, TNF-α) and T cell surface molecule (IL-2 receptor. CD28, CTLA-4) gene expression in two way mixed lymphocyte cultures (MLC) enhanced by concanavalin A (ConA) to assess whether this is a useful predictive method for severe graft-versus-host disease (GVHD) and graft failure in allogeneic bone marrow transplantation (allo BMT) patients. Our present study revealed increased mRNA expression of IL-2, IL-5 and IFN-y using this assay in patients with delayed engraftment followed by graft failure and patients who developed grade III acute GVHD. Elevated IL-2 and IFN-γ levels in MLC medium were also observed in these patients. Concerning T cell surface molecule gene expression in our modified MLC. IL-2 receptor gene expression was not altered so much in allo BMT patients, however, CD28 and CTLA-4 gene expression were elevated in patients with graft failure and severe acute GVHD. The elevated expression of cytokines (IL-2. IL-5 and IFN-y) and T cell surface molecules (CD28 and CTLA-4) mRNA in our modified MLC, in patients who developed severe lethal transplantation-related complications may suggest an important role for these molecules in inducing a strong alloresponse. Therefore, the detection of increased gene expression of those molecules, in our modified MLC system, appeared to be useful for predicting transplantation-related complications in allo BMT patients. In addition. this modified MLC assay may also be useful for the selection of the most compatible related and unrelated donors.

Key Words:

• bone marrow transplantation (BMT)
• cytokine
• CD28
• graft-versus-host disease (GVHD)
• mixed lymphocyte culture (MLC)
• CTLA-4