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American Journal of Pathology, Vol 111, 174-183, Copyright © 1983 by American Society for Investigative Pathology

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Depletion of lymphoid tissues by tilorone. Ultrastructure and synergistic interaction with antilymphocyte serum

S Levine, P Cacho, R Sowinski and WL Thelmo

Antilymphocyte serum (ALS) caused lymphocyte depletion and shrinkage of thymus-dependent areas in spleen and lymph nodes of rats. Tilorone also depleted T lymphocytes, but light- and electron-microscopic examination revealed hyperplasia and vacuolation of the interdigitating cells that remained in the thymus-dependent areas, rather than shrinkage. These changes were not mediated by the adrenal gland. The combination of agents had a synergistic effect on the thymus-dependent areas in the spleen, lymph nodes, Peyer's patches, and bronchial-associated lymphoid tissue, all of which were severely depleted but maintained their normal dimensions. The combination of ALS and a tilorone analog that was capable of depleting lymph node but not spleen, gave a synergistic effect only in lymph node and not in spleen. Tilorone effects were transient, whereas ALS produced a long-lasting depletion. Administration of the two drugs at different times were synergistic only during the brief period of tilorone's effectiveness. The synergistic effects on T lymphocytes correlated well with immunosuppressive potency of the combined drugs on a T-lymphocyte- mediated auto-immune disease.