Studies of congenitally immunologically mutant New Zealand mice. VII. The ontogeny of thymic abnormalities and reconstitution of nude NZB/W mice

The thymus of New Zealand (NZ) mice undergoes premature degeneration both in vitro and in vivo. This involution has often been correlated with the age-dependent loss of NZ mice T helper function. To further define the ontogeny of these events the growth of NZ fetal and neonatal thymus and thymic epithelial cells were studied and compared with BALB/c controls using the techniques of anterior corneal chamber transplantation, organ culture, and tissue culture. NZB fetal thymus, including functional studies of thymic epithelial cells, was similar to BALB/c fetal thymus. In contrast, tissue culture of neonatal NZB, but no BALB/c, thymic epithelium underwent premature degeneration and failed to demonstrate functional activity. The relationships between age-dependent T cell deficiencies were further studied by attempting to reconstitute 4-wk-old NZB/W congenitally athymic (nude) mice using spleen cells from serially aged NZB/W nu/+ controls. Fourweek-old, but not 8-mo-old, NZB/W nu/+ spleen cells reconstituted the response of NZB/W nude mice to SRBC and increased the frequency of spleen cells with T cell markers. However, when adherent cells were depleted from 8-mo-old NZB/W spleen cells, reconstitution of NZB/W nude recipients was again noted. The adherent suppressor cell population of older NZB/W nu/+ mice was also observed in older NZB/W nude mice. Finally, spleen cells, including enriched splenic T and B cells, from autoantibody-producing NZB/W nu/+ animals were unable to transfer sustained production of antibodies to dsDNA when injected into NZB/W nude recepients. The acquired T helper cell deficiency to older NZB/W mice appears secondary to the presence of splenic macrophage suppressor cells and is unrelated to the premature degeneration or involution of thymus or thymic epithelial elements. Finally, NZB/W nude mice are not susceptible to tranfer of autoimmune disease by 'educated' T cells, and the survival of T cell reconstituted NZB/W nude mice is similar to nonreconstituted controls.