ONTOGENY OF MACROPHAGE RESISTANCE TO MOUSE HEPATITIS IN VIVO AND IN VITRO

Gallily, Ruth; Warwick, Anne; Bang, Frederik B.

Increasing resistance to virus infections with age is a well recognized but poorly understood phenomenon (9) . It has been demonstrated in chick embryos to equine encephalomyelitis (10) . and in mice to vesicular stomatitis (11, 12) , and to herpes viruses (13). Recently, Johnson has suggested that there is a cellular basis for the increase with age of the resistance of mice to herpes simplex virus (14). He has shown that virus spreads much more easily in cultures of suckling mouse macrophages than it does in similar cultures of macrophages from adult mice. We have not demonstrated in mouse hepatitis what the nature of the cellular resistance is, but have found that susceptibility, although correlated with the age of the mouse from which it is taken, may be modified by the extent of growth of the culture. Thus, the more rapidly growing cells obtained from younger mice create conditions of greater susceptibility on a mass basis alone, and precautions must be taken to avoid this effect. In our experiments it was not possible to count the number of cells, since we dealt with explants of liver tissue which contained the susceptible macrophages. However, cultures which produced relatively few macrophages were eliminated from all experiments, and only cultures containing roughly comparable numbers of macrophages as judged visually were used. In addition, resistant cells have been routinely obtained from adult (weaned) C,t-I mice, and susceptible cells from infant C,I-I mice. The exact time of transition to resistance is however difficult to determine but cells from mice of 16 days or more of age have not been found susceptible.