CLINICAL-SIGNIFICANCE OF SELECTIVE DECLINE OF DONOR-REACTIVE IL-2-PRODUCING T-LYMPHOCYTES AFTER RENAL-TRANSPLANTATION

Limiting dilution analysis technique was used to enumerate the circula ting precursor frequency of donor and third-party-reactive helper T ly mphocytes (HTLpf) in 28 renal allograft recipients before (pre-tx) and at three intervals (T1: 60-90 days, T2: 120-180 days, T3: 360-1620 da ys) after transplantation (post tr). Two patterns of responses were id entified, in group 1 (n = 12),a five to 31-fold reduction of donor-rea ctive HTLpf (ranging from 1/19231-1/62500) occurred within 90-1620 day s post-tx while in group 2 (n = 16), no significant changes of donor-r eactive HTLpf were seen. In both groups, the third-party-reactive HTLp f in most of these patients remained largely unchanged throughout the study period. The number of HLA-DR mismatches, total number of rejecti on episodes, serum creatinine levels, and biopsy findings at T3 were c ompared in both groups using Fisher's exact probability, and the Mann- Whitney test. We found that 11 patients (92%) in group 1 were HLA-DR c ompatible with donors, while nine (56%) patients in group 2 were HLA-D R compatible with donors, p = 0.04. Ln group 1 eight rejection episode s occurred in five (41.6%) patients during the study period, compared to 33 in 13 (81%) patients in group 2,p = 0.03. Group 1 had a signific antly lower serum creatinine level (at n); median: 136 vs 165 mu mol/l for group 2,p = 0.03. Biopsy indicated no rejection (at n) in eight ( 66%) patients in group 1 as compared to three (18%) patients in group 2,p = 0.03. Taken together, these results indicate that the frequency of circulating HTLpf correlate with the clinical status of the graft. Therefore monitoring of HTLpf in the peripheral blood could be useful in predicting graft outcome and selecting patients for reducing immuno suppression.