Mechanisms of lymphocytic choriomeningitis virus-induced hemopoietic dysfunction.
Results of this study showed that lymphocytic choriomeningitis virus infection causes a marked activation of natural killer (NK) cells not only in the spleen but also in the bone marrow. This activity reached its peak at about day 3 of infection and declined after days 6 to 7. Enhanced NK cell activity was found to correlate with decreased receptivity for syngeneic stem cells in bone marrow and spleen, with the notable exception that decreased receptivity persisted longer in bone marrow. Treatment of infected recipients with anti-asialo GM1 (ganglio-N-tetraosylceramide) significantly increased the receptivity for syngeneic hemopoietic cells. These findings are consistent with the hypothesis that NK cell activation causes rejection of syngeneic stem cells, thus resulting in hemopoietic depression. To understand the mechanisms behind the prolonged decrease in bone marrow receptivity (and bone marrow function in the intact mouse) mentioned above, we followed the changes in the number of pluripotential stem cells (CFU-S) circulating in the peripheral blood and in endogenous spleen colonies in irradiated mice, the limbs of which were partially shielded. It was found that following a marked early decline, both parameters increased to normal or supranormal levels at about day 9 after infection. Because the bone marrow pool of CFU-S is only about 20% of normal at this time after infection, a marked tendency for CFU-S at this stage in the infection to migrate from the bone marrow to the spleen is suggested. It seems, therefore, that as NK cell activity declines, the spleen regains the ability to support growth of hemopoietic cells and the bone marrow resumes an elevated export of stem cells to the spleen. This diversion of hemopoiesis could explain both the long-standing deficiencies of the bone marrow compartment and the prolonged decrease in the receptivity of this organ.
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001853:Bone Marrow / Q000503:physiopathology; D002465:Cell Movement; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000502:physiology; D007111:Immunity, Cellular; D007116:Immunization, Passive; D007694:Killer Cells, Natural / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000503:physiopathology*; D008217:Lymphocytic choriomeningitis virus / Q000472:pathogenicity*; D051379:Mice; D013154:Spleen / Q000503:physiopathology
D000954:Antigens, Surface