Analysis of T cell responses in liver allograft recipients. Evidence for deletion of donor-specific cytotoxic T cells in the peripheral circulation.

Abstract

Analysis of cell-mediated lympholysis in long-term liver allograft recipients indicated that there was a donor-specific unresponsiveness that could not be reversed by the addition of rIL-2 and/or mixed lymphocyte culture supernatant or by nonspecific stimulation ofthe cultures with PHA. Stimulation ofrecipient cells with semisyngeneic cells having both donor and thirdparty HLA antigens failed to reveal the presence of cytotoxic T cells (CTL) specific to the donor, whereas the CTL response to third-party antigens remained normal. Removal of B lymphocytes from the responding cell population did not influence the responses. Furthermore, limiting dilution analysis showed that the liver transplant recipients did not have detectable levels of CTL precursors (Clip) reactive to the donor antigens, whereas their CTLp to third-party antigens remained normal. Donor-specific ClTLp were present before and during the early post-transplant period; these cells were eliminated from the peripheral circulation by 10 mo after transplantation. Taken together, these results indicate that there is a deletion of CTLp specific to donor MHC antigens in the peripheral circulation of long-term liver allograft recipients that may account in part for the success of liver transplantation across MHC barriers. (J. Clin. Invest. 1993. 91:900-906.)

Calcineurin Inhibitor Withdrawal in Stable Kidney Transplant Patients Decreases the Donor-Specific Cytotoxic T Lymphocyte Precursor Frequency

“…For instance, the induction of AICD by Fas-FasL pathway requires previous priming of T cells by IL-2 (28). It has been shown that in long-term liver allograft recipients a donor-specific CTL response was absent in the peripheral blood and could not be reversed by the addition of rIL-2 (29). Preliminary results show that in our patients CD8 ϩ T cells do indeed get activated and proliferate to donor antigens.…”

Donor-specific CTL frequencies in peripheral blood in relation to graft vascular disease after clinical heart transplantation

“…Several studies have demonstrated that a reduction in circulating CTL is associated with stable engraftment [2,3,9]. Interestingly, our study suggests that in patients with stable engraftment who remained free from GVD, no consistent reduction in circulating pCTL numbers was observed over time.…”

“…Because functional tests in the graft, necessitating culturing graft-infiltrating lymphocytes, are invasive and time consuming, we performed experiments in peripheral blood. Several studies have demonstrated that a reduction in circulating CTL is associated with stable engraftment after kidney, liver, and heart transplantation [2,3,91. Therefore, we wondered whether the frequency of CTL in PBMC (peripheral blood mononuclear cells) might also reflect an unstable situation, as in GVD.…”

Thymectomy Impairs but Does Not Uniformly Abrogate Long-Term Acceptance of Semi-Identical Liver Allograft in Inbred Miniature Swine Temporarily Treated With Fk506

“…Activation-induced cell death phenomena in the liver have been reported, and this T-cell exhaustion is known as the "killing field hypothesis" (18 -20). The incoming alloreactive T cells are activated by alloantigens in the liver allograft but encounter the intrahepatic killing mechanisms and are eliminated leaving the graft intact (20,21). The liver is also a hematopoietic organ and provides a microenvironment able to support growth of donor and host cells (22).…”