Effects of drugs on immune responsiveness in rabbits.

The effects of chemotherapeutica: 6 mercaptopurine (6 MP), nitrogen mustard (HN2) and cyclophosphamide (Cy) on T and B cells were studied in standardized experimental systems. From the histological and immunological results it was concluded that: (a) A course of 9 daily 6 MP injections affected antibody production only when given after antigenic stimulation. Histologically figures of mitotic death were found among proliferating cells of plasmacellular-germinal centre-and specific cellular reactions. It was concluded that a net mitotic death of 50% would account for the observed immunological and histological effects; (b) HN2 and Cy affected antibody production itself when administered during a very restricted period (1 through 3 days after ag.). Histologically only morphological changes were found in differentiating immature plasmacells and interphase death of cells involved in germinal centre reactions. Loss of responsiveness depended on the degree of interphase death of follicular elements. Cy interfered with the formation of T helper cells in thymus-dependent antibody production; (c) L-Asparaginase (1,000 U) only prevented the origination of T-helper cells. Neither antibody-producing cells nor their precursors were affected.