Factors affecting the autologous mixed lymphocyte reaction in kidney transplantation
Kyriakides, George K.
Miller, Jody C.
SourceJournal of Clinical Investigation
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In long-term well adapted kidney transplant recipients we have found a close correlation between the T helper (T(H)):T suppressor/cytotoxic (T(S/C)) subset ratios and the presence of T cells that respond in the autologous mixed lymphocyte reaction (AMLR). In 21 recipients with T cell E rosette levels ranging between 53 and 86% and T(H):T(S/C) ratios between 0.15 to 2.10, ratios of > 0.8 correlated with AMLR responses (13/13), and ratios of < 0.8 with AMLR nonreactivity (7/7). By contrast, the allogeneic MLR showed no apparent correlation with the T(H):T(S/C) ratios or with the AMLR pre- or postoperatively. It was found that the AMLR in 22 of 23 normal individuals was markedly inhibited by autologous T cells obtained from peripheral blood lymphocytes, exposed to 3,000 rad (Tx) and added as a third component to the cultures. In contrast, 13 of 13 kidney transplant recipients failed to exhibit this Tx AMLR inhibitory cell population. The 'naturally occurring' T inhibitory cells, fractionated by an affinity column chromatography procedure into x-irradiated T(H) and T(S/C) subsets, inhibited the AMLR to the same extent as unseparated Tx cells. In cell interchange studies performed in four of five HLA identical donor-recipient AMLR (immunosuppressed), but recipient Tx cells failed to inhibit the donor AMLR. Finally T cells, primed in AMLR and allogeneic MLR for 10 d were tested for AMLR or allogeneic MLR inhibitory activity. Allogeneic MLR primed x-irradiated cells, inhibited both the AMLR and allogeneic MLR while AMLR x-irradiated primed cells inhibited neither reaction. The Tx AMLR inhibitor found in normal peripheral blood, appears to be a cell that is highly sensitive to the effects of biologic or pharmacologic immunosuppressive agents.