The effect of cyclophosphamide on immunological memory.
The intradermal injection of bovine gammaglobulin (BGG) anti-BGG immune complexes, in antibody excess, in Freund's complete adjuvant, induced strong delayed hypersensitivity and a state of priming which was recognized by an antihapten and anticarrier humoral immune response following injection of DNP9-BGG nine days later. Cyclophosphamide (CY), given either as small multiple doses over the first seven days after sensitization, or as a single dose on various days, had a strongly selective effect on the antihapten and anticarrier response. The drug treatment, using multiple doses, suppressed the development of a priming for the antihapten IgG2, but not for IgG1 production. Pretreatment with a large dose of CY (250 mg/kg) led only to an enhanced production of anti-DNP IgG2 and not of IgG1 antibodies. This suggests that CY inhibits the suppressor cells regulating the IgG2, but not the IgG1, antibody response. CY, given on day +3 but not on days 0 and +7 impaired both the IgG1 and the IgG2 response. Anticarrier-specific IgG1 could not be detected and the IgG2 was completely suppressed by the drug, given either as multiple doses or as a single large dose administered on days 0, +3 or +7. The selective influence of CY given about the time of the initial immunization suggests that the IgG1 and IgG2 responses involve memory cells with different susceptibilities to CY. Moreover, these memory cells appear to have a different susceptibility to CY as compared with that of the effector cells involved in delayed hypersensitivity.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D003520:Cyclophosphamide / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006968:Hypersensitivity, Delayed; D007074:Immunoglobulin G / Q000096:biosynthesis; D007156:Immunologic Memory / Q000187:drug effects*; D008297:Male; D013997:Time Factors; D005719:gamma-Globulins / Q000276:immunology
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; C030730:dinitrophenyl gamma globulin; D005719:gamma-Globulins; D003520:Cyclophosphamide