Quantitation of cyclosporine-sensitive and -resistant allospecific cytotoxic cells at birth

Abstract

In the absence of clinically relevant models of acute rejection we have attempted to develop an assay to measure cyclosporine-resistant allospecific cytotoxic cells in vitro, beginning at birth. The principle of limiting dilution analysis was applied to investigate umbilical cord bloods as responders. Responders were incubated for 1 h in different concentrations of cyclosporine and irradiated HLA mismatched stimulator cells from healthy adults added, followed by recombinant IL-2. After 7 days, responders were tested against three europium-labelled PHA blasts: stimulator, responder and third party. A significant number of cyclosporine-resistant allospecific cytotoxic cell precursors were found in cord blood indicating prior activation. They may have been primed in utero against non-inherited maternal HLA antigens. Cyclosporine-resistant allospecific cytotoxic cell precursors were demonstrated in human umbilical cord blood using a quantitative assay. These cells may influence the reaction to subsequent transplants.

Does the risk of acute rejection really decrease with increasing recipient age?

“…But, many complications in older recipients might be avoided by more modest immunosuppressive therapy. We have shown in pilot studies that there is a dramatic change in the efficacy of calcineurin inhibitors with age as measured in an in vitro model of acute rejection, exemplified elsewhere [6]. Several mechanisms might explain the weakening of acute rejection with increasing age, including increased sensitivity to immunosuppression.…”