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

James M. Mathew, J. Wallis Marsh, Brian Susskind, T. Mohanakumar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

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 of the cultures with PHA. Stimulation of recipient 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 (CTLp) reactive to the donor antigens, whereas their CTLp to third-party antigens remained normal. Donor-specific CTLp 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.

Original languageEnglish (US)
Pages (from-to)900-906
Number of pages7
JournalJournal of Clinical Investigation
Volume91
Issue number3
DOIs
StatePublished - Mar 1993

Keywords

  • Cell-mediated lympholysis
  • Limiting dilution analysis
  • Liver transplantation
  • Mechanism
  • Peripheral tolerance

ASJC Scopus subject areas

  • Medicine(all)

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