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 = 10), 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.
Crosbie
O M
OM
Liver Unit and Education and Research Centre, St. Vincent's Hospital, Elm Park, Dublin, Ireland.
Costello
P J
PJ
O'Farrelly
C
C
Hegarty
J E
JE
D000328:Adult; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000276:immunology*
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens