Evidence that X-irradiation and 4-hydroperoxycyclophosphamide affects different lymphocytes that respond to specific antigen in vitro.
The present study examined the effect of pulse treatment with the in vitro active synthetic derivative of cyclophosphamide (CY), 4-hydroperoxycyclophosphamide (4-HPCY), and exposure to X-irradiation on the in vitro Concanavalin A (ConA), lipopolysaccharide (LPS), and antigen-specific blastogenic responses of in vivo-primed lymph node cells. Primed lymph node cells from CY-pretreated, aggregated (A) human IgG-complete Freund's adjuvant (AHGG-CFA)-immunized mice were untreated, exposed to various doses of irradiation, or pulse treated with different concentrations of 4-HPCY before being cultured in medium alone or in medium containing HGG, ConA, or LPS. The results show that HGG-responding and LPS-responding cells exhibited similar dose-inactivation profiles following exposure to irradiation or pulse treatment with 4-HPCY. More than 75% of reactivity was eliminated by exposure to 100 rads or pulse treatment with 20 microM 4-HPCY. In contrast to preculture pulse treatment with 4-HPCY, however, when primed lymph node cells were cultured in medium containing 4-HPCY (culture treatment) LPS-responding cells were shown to be more sensitive to inactivation than HGG-responding cells. The data further show that the effect of low-dose irradiation and of culture treatment with 4-HPCY on the HGG-specific response of primed lymph node cells was additive, suggesting that these agents inactivate different cell subtypes that contribute to the HGG-specific response in vitro.
Clark
C
C
LaSota
I
I
Borch
R F
RF
D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D003208:Concanavalin A / Q000494:pharmacology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D004307:Dose-Response Relationship, Radiation; D000939:Epitopes; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology; D007700:Kinetics; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000528:radiation effects; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL
D000941:Antigens; D000939:Epitopes; D007074:Immunoglobulin G; D003208:Concanavalin A; D003520:Cyclophosphamide; D005620:Freund's Adjuvant; C011272:perfosfamide