Increase in NK cell number and turnover rate during acute viral infection

Abstract

NK cell turnover and division during infection of mice with lymphocytic choriomeningitis virus (LCMV) was examined. Treatments with hydroxyurea (HU), a drug specific for cells synthesizing DNA, had no effect on control spleen NK cells, but significantly reduced NK cell-mediated lysis in LCMV-infected mice. When HU was administered at 9 and 2 hr before spleen cell harvest, the augmented lysis mediated by NK cells isolated from LCMV-infected mice was only 40% of that mediated by NK cells isolated from LCMV-infected untreated mice. Spleen cells that had been pulse-labeled with [3H]thymidine were used in a single cell assay with autoradiography to detect lysis mediated by blast cells. HU eliminated blast-NK cells; 34% of activated NK cell killing was mediated by blast cells, whereas less than 12% of the reduced NK cell activity after HU treatments was blast cell-mediated. The NK cells activated in vivo had lower densities than control NK cells. Although the total cell yields from control spleens and spleens on day 3 post-infection with LCMV were similar, low density Percoll gradient fractions from the day 3 spleen cell preparations contained three times as many cells as equivalent fractions from control populations. The same low density fractions were enriched in NK cell activity and in blast-NK cells. Activated spleen cell populations also contained increased numbers of large granular lymphocytes. These data indicate that NK cells have increased turnover rates during viral infection, that this increase in turnover is accompanied by NK cell division, and that this results in increases in the numbers of NK cells.