The mixed lymphocyte culture (MLC) is an established clinical method for bo
ne marrow transplantation, as it serves as an in vitro model for allogenic
reaction and transplantation. We previously showed that cytokine release in
to the supernatant is a more specific and sensitive parameter for cross-rea
ctivity in the MLC than the common measurement of cell proliferation. There
fore we tried to find an inhibitor of the MLC in vitro with the least side
effects in vivo, measuring interferon (IFN)-gamma as one of the most import
ant cytokines in posttransplant medicine. Earlier studies showed that zinc
is an important trace element for immune function with both stimulatory and
inhibitory effects on immune cells. We found that slightly elevated zinc c
oncentrations (three to four times the physiological level), which do not d
ecrease T-cell proliferation in vitro nor produce immunosuppressive effects
in vivo, suppress alloreactivity in the mixed lymphocyte culture. In this
report we analyzed the mechanism whereby zinc influences the MLC to possibl
y find a nontoxic way of immunosuppression.