Ontogenic development of contrasuppression.

Using a xenogeneic graft-versus-host assay system, we have been able to document the sequential appearance of certain regulatory cells in newborn mice. Before birth, mouse spleen cells exhibit potent suppression that cannot be ameliorated by contrasuppressor cells. On the day of birth, the spleens contain equally potent suppressor cells, but these cells now can be inhibited totally by contrasuppressor cells. Between days 1 and 2 after birth, suppression, as picked up by our system, has disappeared. However, it can be found hiding behind contrasuppressor cells, as elimination of the latter cells with appropriate antisera reveals cells with the same suppressive potency as spleen cells taken 1 or 2 days earlier. Further, if the thymus is removed on the day of birth or 1 day later, the suppressor-obscuring cells do not appear. Thus, there appears to be an inherent ontogenic schedule that the thymus follows, which determines the time when different regulatory cells will emerge from it.