Development of graft-vs.-host disease-like syndrome in cyclosporine- treated rats after syngeneic bone marrow transplantation. I. Development of cytotoxic T lymphocytes with apparent polyclonal anti-Ia specificity, including autoreactivity

Activation of Anti-la-reactive Cells? The data presented above demonstrate that splenic T cells of rats with syngeneic GVHD were capable of lysing blast cells from several strains of rats. Lysis was mediated by a T cell with the OX8 phenotype, not expressing the W3/25 antigen, and it appeared to recognize Ia or class II determinants. To determine whether lysis was mediated by one cell recognizing multiple specificities and/or a shared determinant, or whether there was polyclonal activation of anti-Ia-reactive lymphocytes, a series of cold targetinhibition studies was undertaken. Fig. 4 gives the results of a representative experiment in which both ACI and Lewis cold targets (blast cells) were added at various concentrations to lytic assays using either ACI-or Lewis-labelled targets. The results demonstate that the ACI and Lewis cold targets were equally effective at inhibiting lysis when added to the CML assay with the labelled Lewis targets. Comparable findings were observed in that cold ACI and Lewis targets were equally effective at inhibiting the lysis of labelled ACI target cells. In a series of three other experiments, comparable results were observed, with no significant difference between cold ACI or Lewis target cells in their ability to inhibit lysis Hot'Cold Torget Ratio F]CURE 4. Cold target inhibition studies were performed using untabelled ACI and/or Lewis PHA blast cells. The cold targets were added in graded quantities to CML assays using either S~Cr-labelled ACI or Lewis blast cells. Nylon wool-nonadherent spleen cells from a CsAtreated syngeneic marrow transplant recipient with the GVHD-Iike syndrome were used as effector cells. Effector/target ratio was 100:1.