Blastogenesis of natural killer cells during viral infection in vivo
Biron, C.A.; Welsh, R.M.
Journal of Immunology 129(6): 2788-2795
1982
ISSN/ISBN: 0022-1767 PMID: 7142707 Document Number: 183287
The induction of dividing NK was examined. In contrast to endogenous NK cells, which were contained within a small- to medium-size class after separation by centrifugal elutriation, activated NK cells had a broad size distribution and were found in large, blast-size classes. The blast-size effector cells expressed the NK antigens asialo GM1 and NK 1.2. Short-term interferon activation of spleen cells from uninfected mice in vitro or in vivo did not greatly augment the lysis mediated by large-size cells, indicating that the blast-size NK cells were generated during infection. Blast-size NK cells were not found in irradiated infected animals, suggesting that the induction of these cells required cell division. Blast-size NK cells were readily elicited in athymic nude mice; the generation of these cells was thus independent of thymic function. To directly visualize lysis mediated by dividing NK cells, effector cells pulsed with 3H-thymidine were conjugated to target cells and used in a single-cell assay in agarose with autoradiography. Of the lysis by endogenous NK cells, < 1% was mediated by blasts. On the 3rd day after LCMV infection NK cell lysis peaked and at least 20% of the killing was directly mediated by blast cells. By day 7 postinfection, NK cell activity and blast cell-mediated killing had declined. The blast cells from day 3 postinfection that formed conjugates were a unique population of dividing cells; 45% of day 3 blast cells in conjugates were killer cells, but on day 0, < 1% and by day 7, only 5% of blast cells bound to target cells mediated lysis. A proportion of the NK cell activation observed during viral infection is thus dependent upon the induction of NK-blast cells. This indicates either that control endogenous NK cells are induced to undergo blastogenesis or that blastogenesis and maturation of pre-NK cell populations occur concomitantly. Proliferation of the population as well as interferon activation of NK cells or NK cell precursors apparently contribute to the total augmentation of NK cell activity by virus infections in vivo.