Induction therapy including antithymocyte globulin induces marked alterations in T lymphocyte subpopulations after liver transplantation: results of a long-term study

Various immunosuppressive regimens aim to reduce the incidence of acute rejection after liver transplantation. The efficacy of antithymocyte globulin (ATG) induction therapy and short-term effects on the cellular response have been demonstrated in several studies. Nevertheless, information about long-term effects of ATG therapy on cellular responses and frequency of complications is limited. Therefore, we analyzed the effect of ATG administration within a cyclosporine-based induction therapy, including azathioprine and prednisolone, on lymphocyte subsets and activation markers. We divided 35 liver transplant recipients into two groups according to their initial postoperative immunosuppression: a triple group without (n=15) and a quadruple group with ATG (n=20). The minimum observation time (flow cytometry analysis, clinical follow-up) was 2 years. Patients treated with ATG had persistently lower percentages of T cells for at least 2 years postoperatively (P<0.001). The CD4/CD8 ratios were lower in the quadruple group (P<0.005). The patients in the ATG group revealed a drop in CD25+ T cells within 2 years (P<0.05). However, the percentage of CD71+ and HLA-DR+ T cells was temporarily higher in patients with ATG treatment (P<0.05). Patients with ATG treatment showed persistently higher levels of CD8+/CD57+ double positive cells in the late postoperative phase (P<0.05). In contrast, no differences could be observed between the two groups for major parameters of clinical outcome (acute rejections, severe infections, patient survival). We conclude that ATG therapy induces long-lasting alterations in T-cell subset composition. However, no beneficial clinical effect could be confirmed after liver transplantation.