In vitro evidence for defective afferent immune function in long-term renal allograft recipients

Experiments were designed to evaluate afferent immune functions in 21 long-term (greater than or equal to 3 years) 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 (means = 84,789 +/- 8242) that were comparable to those exhibited by normal controls (means = 86,082 +/- 7423). Likewise, mean responses in the AMLR were similar in recipients and controls (14,937 +/- 3243 versus 16,101 +/- 3005), although a greater percentage of recipients generated AMLRs below 5000 cpm than did normals (8/21 versus 4/20). However, 13 recipients analyzed for responsiveness to tetanus toxoid were shown to generate mean proliferative responses that were significantly depressed below normal (18,095 +/- 5545 versus 48,935 +/- 8813, P less than 0.001). Furthermore, despite significant proliferation in the AMLR means = 27,648 +/- 5168), 8 recipients generated significantly lower CTL activity in AMLR cultures than normal controls (mean percentage of cytotoxicity = 10.3 +/- 4.7 versus 24.9 +/- 4.7, P less than 0.05). These recipients generated normal CTL levels against allogeneic target cells following stimulation in an allo-MLR. Thus, these studies provide experimental support for the existence of altered T helper cell-mediated functions in long-term renal allograft recipients.