INVITRO EVIDENCE FOR DEFECTIVE AFFERENT IMMUNE FUNCTION IN LONG-TERM RENAL-ALLOGRAFT RECIPIENTS

Experiments were designed to evaluate afferent immune functions in 21 long-term (.gtoreq. 3 yr) renal allograft recipients by using in vitro assays that included autologous and allogeneic mixed lymphocyte reactions (AMLR and allo-MLR), proliferative responses to a soluble antigen (tetanus toxoid), and the ability to generate cytotoxic T lymphocytes (CTL) following stimulation in an AMLR. The results showed that allograft recipients generated responses in the allo-MLR (.hivin.x = 84,789 .+-. 8242) that were comparable to those exhibited by normal controls (.hivin.x 86,082 .+-. 7423). Mean responses in the AMLR were similar in recipients and controls (14,937 .+-. 3243 vs 16,101 .+-. 3005), although a greater percentage of recipients generated AMLR below 5000 cpm [cells/ml] than did normals (8/21 vs 4/20). Recipients (13) analyzed for responsiveness to tetanus toxoid were shown to generate mean proliferative responses that were significantly depressed below normal (18,095 .+-. 5545 vs 48,935 .+-. 8813, P < 0.001). Despite significant proliferation in the AMLR (.hivin.x = 27,648 .+-. 5168), 8 recipients generated significantly lower CTL activity in AMLR cultures than normal controls (mean percentage of cytotoxicity = 10.3 .+-. 4.7 vs 24.9 .+-. 4.7, P < 0.05). These recipients generated normal CTL levels against allogeneic target cells following stimulation in an allo-MLR. These studies provide experimental support for the existence of altered T helper cell-mediated functions in long-term renal allograft recipients.