Immune responses to organ allografts. III. Marked decrease in medullary thymocytes and splenic T lymphocytes after cyclosporin A treatment

Abstract

Untreated LEW rats reject primarily vascularized Ag-B-incompatible LBNF1, BN, and WF cardiac allografts in 6 to 8 days. Cyclosporin A (CyA) administered 15 mg/kg/day i.m. for 7 days after grafting extends graft function greater than 100 days. Histological studies demonstrated that CyA treatment strikingly reduces the size and cellularity of the thymic medulla, splenic marginal zone, and splenic periarterial sheath by 97, 67 and 50%, respectively. These compartments are thought to contain cells of a single T lymphocyte lineage with helper and cytotoxic functions. CyA was less effective against cells in the thymic cortex and splenic red pulp, compartments thought to contain suppressor cells. CyA-induced depletion of lymphoid tissues was maximal 7 to 14 days after completion of treatment. All compartments recovered nearly normal morphology by 50 to 100 days, although hyperplastic nodules were found in spleens of three WF heart graft recipients during the recovery phase. CyA was more effective, histologically, in inhibiting the immune response to heart grafts from WF than from LBNF1 or BN donors. Within 3 days after LBNF1 or BN heart grafting, moderate antibody production occurred in the spleen (as noted by increase in Ig-positive immunoblasts) and vascular damage occurred in the grafts. These signs of rejection were delayed until 14 days in WF heart grafted rats. In none of the strain combinations were these early reactions followed by a vigorous cellular infiltrate. Thus, CyA seems to decrease preferentially cytotoxic and helper T lymphocyte responses to cardiac allografts.