T-lymphocyte subsets in renal allograft recipients treated with cyclosporine and azathioprine.

Thirty-nine renal allograft recipients were prospectively studied to determine the quantitative effects of different immunosuppression protocols on T-cell subsets (total lymphocytes [T3], helper/inducer [T4] and suppressor/cytotoxic [T8]). Eighteen patients were initially immunosuppressed with only azathioprine and prednisone but required subsequent treatment for rejection by the addition of antithymocyte globulin (ATG) (Upjohn, Kalamazoo, MI) or conversion to cyclosporine. Three of these patients had ATG-resistant rejections and were treated with the monoclonal antibody ORTHO OKT3 (ORTHO Pharmaceuticals, Raritan, NJ). Twenty-one patients were treated only with cyclosporine and prednisone. Plasma levels of cyclosporine, as determined by high-performance liquid chromatography, were kept in the range of 50-100 ng/mL (mean: 78.1 +/- 52.1). One patient had a lymphoma, two patients had failed grafts, and three patients converted their cytomegalovirus titers. The results demonstrate that the immunosuppressive agents, azathioprine, prednisone, and cyclosporine, have an additive effect in depressing the T-lymphocytes and their subsets. In addition, ATG and cyclosporine had a more selective ablation of the T4 subset, resulting in a reversal of the T4/T8 ratios. This depression was independent of the plasma level of cyclosporine. Finally, the pan T-cell monoclonal antibody OKT3 led to severe depletion of all T-cell subsets but resulted in a normal T4/T8 ratio. In conclusion, immunosuppressive agents have a variable effect on T-lymphocytes and their subsets that cannot be adequately characterized by the T4/T8 ratio alone, but which should be quantitatively assessed by examining all subsets.