Failure of in vitro T-cell assays to predict clinical outcome after human kidney transplantation.
Allotransplant rejection is a T-cell-dependent reaction. Functional in vitro T-cell assays are being used widely for donor-recipient matching in bone marrow transplantation and have recently been used in some centres for transplant monitoring. In order to assess tolerance induction after clinical transplantation, we measured the T-cell response of the host against donor spleen cells of 33 kidney transplant patients before and every 3 months after transplantation over a period of 18 months. The T-cell reactivity before transplantation was not significantly different in any of the assays in rejecting and non-rejecting patients. In the classical mixed lymphocyte culture (MLC), a donor-specific loss of reactivity was seen only in a patient with a CMV-associated irreversible transplant rejection. One patient with chronic rejection acquired a very high MLC response against donor spleen cells and a high response against third-party cells. Little or nonspecific changes were seen in the MLCs of all other patients. Using the method of limiting dilution analysis (LDA), we found a significant reduction of donor-specific cytotoxic T-cell precursors (CTL-p) within the first 3 months after transplantation in most patients with high antidonor CTL-p frequencies before transplantation. The reduction of donor-specific CTL-p was seen in patients with rejection episodes as well as in patients without. Thus we conclude, in contrast to others, that MLC and CTL-p LDA have no predictive value on the outcome of clinical transplantation.
Steinmann
J
J
Institut of Immunology, University of Kiel, Germany.
Kaden
J
J
May
G
G
Schröder
K
K
Herwartz
C
C
Müller-Ruchholtz
W
W
D017637:Clonal Deletion; D006084:Graft Rejection; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D016030:Kidney Transplantation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D007376:Interleukin-2