Long-term suppression of natural killer (NK) cell development in neonatally bone marrow (BM)-transplanted mice

T lymphocytes and NK cells share a common precursor. Whereas T cells are derived from waves of T cell precursors during fetal and neonatal stages, NK cell development during that period is less understood. Moreover, NK cell numbers are very low during that period. This observation seems to contradict the kinetics of NK cell maturation from NK progenitors (7 to 12 days). Here we test the potential of NK cell reconstitution during fetal and neonatal stages. To this end, tge26 mice, which are T and NK cell deficient, were transplanted with progenitor cells. Five weeks later, T and NK cell reconstitutions were compared by flow cytometric analyses and functional assays. T cell development could be reconstituted with the following approaches: In utero injection of fetal liver cells into day 16 tge26 embryos; transferring tge26 fetal thymuses under the kidney capsule of adult tge26 mice followed by BM injection; and BM injection of tge26 neonates. Surprisingly, no NK cell development was observed in these mice. Moreover, RAG-/- BM could reconstitute NK cell compartments when enfused into adult tge26 mice, but did not when injected into neonatal tge26 mice. The latter mice, however, were fully reconstituted in both T and NK cell compartments when they were further transplanted with wild-type BM in adulthood. These data appear to suggest that from day 16 fetal to neonatal stages, NK cell development is suppressed, and this suppression could be long lasting unless it was removed by a second wave of progenitors.