FUNCTION AND MIGRATION OF SUPPRESSOR LYMPHOCYTES FROM CYCLOSPORINE-TREATED HEART GRAFT RECIPIENTS

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Abstract
(LEW [Lewis] .times. BN [Brown Norway]) F1 [rat] cardiac allografts survive more than 100 days in LEW recipients treated with cyclosporine 15 mg/kg i.m. for 7 days only. Transfer of thymocytes (TL) or splenocytes (SL) from these hosts into untreated syngeneic rats significantly prolongs the survival of (LEW x BN)F1 test cardiac allografts (P < 0.001). The subset of T lymphocytes responsible for this effect and its migration patterns were defined. T helper lymphocytes (Th) and T cytotoxic/suppressor cells (Tc/s) were separated from thymus and spleen of cyclosporine-treated recipients using monoclonal antibodies W3/25 and MRC OX8, respectively. The cell subsets were adoptively transferred into syngeneic recipients. TL from cyclosporine-treated, grafted rats significantly improved test graft survival to .apprx. 12-14 days, irrespective of the subpopulation transferred. Unseparated SL as well as T lymphocytes and Tc/s cells also prolonged test graft survival (P < 0.001); transfer of Th or serum was ineffectual. The presence of monoclonal antibody on the surface of the transferred lymphocytes inhibited their function in vivo. Test grafts following transfer of unseparated SL and Tc/s coated with monoclonal antibody were rejected acutely, in contrast to uncoated cells or cells coated with antibody and then treated with pronase. Migration patterns of 3H-adenosine labeled SL, Th and Tc/s adoptively transferred into normal LEW rats were studied. SL and Tc/s, both active in transfer of unresponsiveness from cyclosporine-treated hosts migrated similary, i.e. into lymph nodes and away from spleen of test animals, in contrast to the pattern seen in the control groups. Th-coated and monoclonal-antibody-coated SL were preferentially trapped in the liver. Evidently, Tc/s lymphocytes transfer specific unresponsiveness from cyclosporine-treated and grafted hosts.

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