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-resistant 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.
Stanford
W L
WL
Department of Microbiology and Immunology, Duke University Medical Center, Durham, North Carolina 27710.
Strauss
G H
GH
Finn
O J
OJ
D001379:Azathioprine / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004351:Drug Resistance; D006084:Graft Rejection / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013866:Thioguanine / Q000378:metabolism
D013866:Thioguanine; D001379:Azathioprine