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 ($$3 years) renal allograft recipients by using in vitro assays that included autologous and allogeneic mixed lymphocyte reactions (AMLR and allo-MLR), proliferative responses to a soluble antigen (tetanus toxoid), and the ability to generate cytotoxic T lymphocytes (CTL) following stimulation in an AMLR. The results showed that allograft recipients generated responses in the allo-MLR ($x=84,789$$8242) that were comparable to those exhibited by normal controls ($x=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$$8813, P < 0.001). Furthermore, despite significant proliferation in the AMLR $x=27,648$$5168), 8 recipients generated significantly lower CTL activity in AMLR cultures than normal controls (mean percentage of cytotoxicity = 10.3$$4.7 versus 24.9$$4.7, P < 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.