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 change‐s 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.