Changes in peripheral blood double-negative T-lymphocyte (CD3+ CD4- CD8-) populations associated with acute cellular rejection after liver transplantation

Circulating CD3+ T lymphocytes that express neither the CD4 nor CD8 surface molecules (double-negative T lymphocytes) are phenotypically and functionally distinct from single-positive CD3+CD4+ and CD3+CD8+ lymphocytes and are thought to represent a distinct T-cell lineage. The presence of low numbers of double-negative T cells in healthy individuals and the increase observed in association with lymphoproliferative disorders, graft-versus-host disease, and autoimmune diseases suggest a pathogenic or immunoregulatory role for this population of T lymphocytes, In this study, peripheral blood double-negative T cells were assessed quantitatively using three-color flow cytometry in 10 patients after liver transplantation during a 6-week period. During this time, 12 episodes of histologically proven acute cellular rejection occurred in 8 patients. The median postoperative baseline double-negative T-cell count expressed as a proportion of the CD3+ T cells was 2.4 +/- 1.2 (median +/- SD; n = In), which was identical to a control group of healthy adults (2.5 +/- 2.4; n = 9), Circulating numbers of double-negative T cells were increased significantly during acute cellular rejection (6.8 +/- 6.7; P < .001; n = 12), After pulse corticosteroid therapy for rejection, there was a significant decrease in the double-negative T-cell population (3.5 +/- 5.0 v 6.8 +/- 6.7; P = .01), No significant changes occurred in the double-negative T-cell count in the absence of clinical events (2.4 +/- 3.5; n = 73). These findings are consistent with a role for double-negative T cells in the initiation of acute cellular rejection or a possible regulatory role in the immunologic changes associated with rejection. Copyright (C) 1998 by the American Association for the Study of Liver Diseases.