Membrane lymphotoxin is required for the development of different subpopulations of NK T cells

The development of lymphoid organs requires membrane-bound lymphotoxin (LT), a heterotrimer containing LT alpha and LT beta, but the effects of LT on T cell function have not been characterized extensively, Upon TCR cross-linking in vitro, splenocytes from both LT alpha(-/-) and LT beta(-/-) mice failed to produce IL-4 and IL-10 due to a reduction in NK T cells. Concordantly, LT alpha(-/-) and LT beta(-/-) mice did not respond to the lipoglycan alpha-galactosylceramide, which is presented by mouse CD1 to V alpha 14(+) NK T cells. Interestingly, both populations of NK T cells, including those that are mouse CD1 dependent and alpha-galactosylceramide reactive and those that are not, were affected by disruption of the LT alpha and LT beta genes. NK T cells were not affected, however, in transgenic mice in which LT signaling is blocked, beginning on day 3 after birth, by expression of a soluble decoy LT beta receptor. This suggests that membrane-bound LT is critical for NK T cells early in ontogeny, but not for the homeostasis of mature cells.