Osteopetrosis associated with premature thymic involution in grey-lethal mice. In vitro studies of thymic microenvironment.
The thymic atrophy developed in osteopetrotic grey-lethal (gl/gl) mouse during the last 10 days of life, and at 35 days of life gl/gl mice had only a few million thymic cells. Maximal survival of gl/gl mice was about 40 days. Earlier, at 20 days of age despite the presence of all signs of osteopetrosis their thymus had normal cellularity. This change in thymus cellularity was associated with relative increase in the frequency of cells forming thymic non-lymphoid (stromal) colonies in vitro. There were no qualitative differences in the presence of major cell types i.e. fibroblastoid, epithelioid and macrophages normally observed in these colonies. However, giant multinucleated cells resembling macrophages in size and appearance of nuclei were observed exclusively in cultures of the thymus from 20 day old control mice and not in cultures of gl/gl mice. On the other hand, in cultures of the thymuses of 35 day old gl/gl mice giant cells were observed that were nearly absent in cultures of the thymuses of control mice. These cells were either polynuclear or their nuclei were segmented and they resembled rather nuclei of epithelioid and fibroblastoid cells than nuclei of macrophages. The significance of all these findings is discussed.