NK cells play an important role in the immune system but the cellular and molecular requirements for their early development are poorly understood. Lymphotoxin-α (LTα)-/- and LTβR-/- mice show a severe systemic reduction of NK cells, which provides an excellent model to study NK cell development. In this study, we show that the bone marrow (BM) or fetal liver cells from LTα-/- or LTβR-/- mice efficiently develop into mature NK cells in the presence of stromal cells from wild-type mice but not from LTα-/- or LTβR-/- mice. Direct activation of LTβR-expressing BM stromal cells is shown to promote to early NK cell development in vitro. Furthermore, the blockade of the interaction between LT and LTβR in adult wild-type mice by administration of LTβR-Ig impairs the development of NK cells in vivo. Together, these results indicate that the signal via LTβR on BM stromal cells by membrane LT is an important pathway for early NK cell development.
ASJC Scopus subject areas
- Immunology and Allergy