Exposure of neonatal female mice to diethylstilbestrol persistently impairs NK activity through reduction of effector cells at the bone marrow level.
Female NMRI mice neonatally treated with diethylstilbestrol (DES) show persistent impairment of various immune parameters, including NK activity. The present study demonstrated that NK activity was reduced in all lymphoid compartments and thus is not due to a simple redistribution of effector cells. Poly I:C was unable to augment NK activity in DES treated animals in vitro and in vivo. This defect was not attributable to inability to produce interferon in response to poly I:C since interferon-beta was also unsuccessful in augmenting NK activity in vitro. Moreover, the lack of response was not dependent on alterations in macrophage function, as evident from experiments showing that macrophages from DES-exposed animals resulted in a normal enhancement of NK activity in response to poly I:C when mixed with lymphocytes from control animals. Studies at the single cell level revealed that the reduced NK activity was the result of a reduced number of target-binding effector cells, and that the individual cells actually binding a target killed the target in an apparently normal fashion. Adoptive transfer of bone marrow cells between control and neonatally DES-treated animals showed that the reduced number of effector cells was determined at the bone marrow level.
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004054:Diethylstilbestrol / Q000494:pharmacology*; D005260:Female; D007116:Immunization, Passive; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007372:Interferons / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008221:Lymphoid Tissue / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D013601:T-Lymphocytes / Q000187:drug effects
D007166:Immunosuppressive Agents; D004054:Diethylstilbestrol; D007372:Interferons