EVIDENCE THAT DRUG-RESISTANT ALLOREACTIVE T-CELLS MAY CONTRIBUTE TO HUMAN GRAFT-REJECTION

The objective of our study was to determine whether resistance to immunosuppressive drugs by transplant recipient’s T cells could contribute to continued graft rejection, in spite of immunosuppressive therapy. The T cell lines used in this series of experiments were originally established from T cells that had infiltrated kidney or liver grafts and initiated rejections in patients receiving immunosuppressive drugs, including the purine analogue azathioprine (AZ). We have used a proliferation assay and the Strauss-Albertini test to analyze the T cell lines. Both assays use 6-thioguanine (6-TG), an amino derivative of AZ, as the selective agent to measure the resistance to AZ. Although the frequency of 6-TG-re- sistant variants in the majority of T cell lines closely resembled the frequency found in peripheral blood lymphocytes of controls, we identified four cell lines that demonstrated virtually complete resistance to the purine analogue 6-TG in both assays. These observations indicate that a more effective immunosuppressive treatment may be achieved by using a combination of drugs. © 1990 by Williams & Wilkins.