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.
Oertel
Michael
M
Department of Clinical Immunology and Transfusion Medicine, University of Leipzig, Germany. moertel@aecom.yu.edu
Sack
Ulrich
U
Kohlhaw
Kay
K
Lehmann
Irina
I
Emmrich
Frank
F
Berr
Frieder
F
Hauss
Johann
J
Schwarz
Rene
R
D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D016516:CD4-CD8 Ratio; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology* / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D011184:Postoperative Period; D012189:Retrospective Studies; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine