Perspectives in patient monitoring.
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Biomedical subjects
Publications and source records attributed to N R Sinclair.
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The short-term kinetics of T cell-mediated cytotoxicity was investigated using a cloning inhibition assay. Murine cytotoxic thymus-derived lymphocytes (CTL) generated in vitro in mixed leukocyte cultures (MLC), were incubated for various periods of time at 37 degrees C with allogeneic mastocytoma target cells. The mixtures were then plated in soft agar, and mastocytoma clone formation was assessed after 5-7 days incubation. Using this technique, it was demonstrated that events leading to the loss of cloning ability could be detected after 1-3 min incubation at 37 degrees C, and after 20-30 min, 95% of the clone forming cells had been inactivated. When these results were compared directly with those obtained using the conventional 51Cr-release assay, it was found that the events leading to loss of cloning ability occurred more rapidly than indicated by the isotope assay. However, a modification of the 51Cr-release assay involving EDTA addition, gave comparable results to the cloning inhibition assay. These results raise the possibility that the events leading to 51Cr-release of tumor target cells may be related in time to those leading to the loss of cloning ability.
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The F(ab')2 fraction of an anti-tumor IgG alloantiserum induced passive enhancement of tumor allografts in inbred mice about as well as did intact IgG; i.e. apparently the Fc fragment is not required for suppressing cellular immunity. Passive F(ab')2, however, was somewhat less efficient than intact IgG or whole alloantiserum in depressing the allohemagglutinin response. The latter finding is in accord with previous observations on the relative inefficiency of F(ab')2 in feedback inhibition of the humoral response of mice to a heteroantigen.
Low doses of irradiation, increased number of T cells, increased T cell activity as in the allogeneic effect, or early activation of an in vitro cell-mediated immune response all confer resistance to antibody feedback. In some of these systems, the resistance is directed against immunosuppression by intact IgG antibody whereas suppression by F(ab')2 antibody is either not changed or increased. These forms of interference with immunosuppression by antibody, are explained in terms of an Fc-dependent model for antibody-feedback regulation.
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Immune responses, specific to the stored donor tissue, were measured in 26 recipients over 4,000 days. CML positive crossmatches were associated with accelerated rejections (three cases). LDA positive crossmatches resulted in primary non-functioning kidneys (three cases). Post-transplantation. CML (16 hour inculation) was associated with rejection (p equals 0.001), highly predictive of rejection (p equals 0.001), and when positive after rejection treatment, was associated with a failure to respond (p equals 0.005 - 0.01). 51Cr-CDA was also associated with rejection (p equals 0.002). Recovery of these immunologic participants from the explanted kidney substantiated that they were important effector mechanisms in vivo.
A patient with preformed cytotoxic lymphocyte-dependent antibody (L.D.A.) against the specific renal transplant donor rapidly rejected the grafted kidney. The characteristics of rejection were not those of hyperacute rejection due to cytotoxic complement-dependent antibody or of acute rejection is attributed to the cytotoxic activity of L.D.A. The avoidance of transplants based on positive crossmatches by the L.D.A. test or at least the carrying out of the L.D.A. crossmatch is advised.
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