Immunological and clinical observations in diabetic kidney graft recipients pretreated with total-lymphoid irradiation.
In a feasibility study, twenty patients with end-stage diabetic nephropathy were treated with fractionated total-lymphoid irradiation (TLI, mean dose 25 Gy), before transplantation of a first cadaveric kidney. During radiotherapy, only one patient had a serious side effect (bone marrow depression). After transplantation four patients died (one of a myocardial infarction, one of ketoacidosis, and two of infections occurring during treatment of rejection crises). One graft was lost because of chronic rejection. The other 15 patients have a functioning graft (mean follow-up 24 months) and receive low-dose prednisone alone (less than 10 mg/day, n = 11) or in conjunction with cyclosporine (n = 4) as maintenance immunosuppressive therapy. A favorable clinical outcome after TLI (no, or only one, steroid-sensitive rejection crisis) was significantly correlated with a high pre-TLI helper/suppressor lymphocyte ratio, a short interval between TLI and the time of transplantation, and the occurrence of functional suppressor cells early after TLI. The most striking immunological changes provoked by TLI consisted of a long-term depression of the mixed lymphocyte reaction and of the phytohemagglutinin, and Concanavalin A or pokeweed-mitogen-induced blastogenesis. A rapid and complete recovery of the natural killer cell activity was observed after TLI. A permanent inversion of the OKT4+ (T helper/inducer) over OKT8+ (T suppressor/cytotoxic) lymphocyte ratio was provoked by a decrease of the OTK4+ subpopulation, together with a supranormal recovery of the OKT8+ lymphocytes. A majority of the latter lymphocytes did also express the Leu 7 and the Leu 15 phenotype.
D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003928:Diabetic Nephropathies / Q000601:surgery*; D005240:Feasibility Studies; D005260:Female; D006085:Graft Survival; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects / Q000379:methods; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation; D008221:Lymphoid Tissue / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D013601:T-Lymphocytes / Q000145:classification / Q000528:radiation effects
D007166:Immunosuppressive Agents