Transplantation-related complications predicted by cytokine gene expression in the mixed lymphocyte culture in allogeneic bone marrow transplants.
In this study, we have investigated cytokine (IL-1 beta, IL-2, IL-5, IL-6, IFN-gamma, TNF-alpha) 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-gamma 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-gamma 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-gamma) 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.
Tanaka
J
J
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Imamura
M
M
Kasai
M
M
Sakurada
K
K
D015703:Antigens, CD / Q000096:biosynthesis; D001483:Base Sequence; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000276:immunology*; D018106:CD28 Antigens / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D017931:DNA Primers; D015870:Gene Expression; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000276:immunology*; D006801:Humans; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000276:immunology*; D008969:Molecular Sequence Data; D011183:Postoperative Complications / Q000453:epidemiology / Q000276:immunology; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
D015703:Antigens, CD; D018106:CD28 Antigens; D016207:Cytokines; D017931:DNA Primers; D012333:RNA, Messenger