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-lin king in vitro, splenocytes from both LT alpha(-/-) and LT beta(-/-) mice fa iled to produce IL-4 and IL-10 due to a reduction in NK T cells. Concordant ly, LT alpha(-/-) and LT beta(-/-) mice did not respond to the lipoglycan a lpha-galactosylceramide, which is presented by mouse CD1 to V alpha 14(+) N K T cells. Interestingly, both populations of NK T cells, including those t hat are mouse CD1 dependent and alpha-galactosylceramide reactive and those that are not, were affected by disruption of the LT alpha and LT beta gene s. NK T cells were not affected, however, in transgenic mice in which LT si gnaling is blocked, beginning on day 3 after birth, by expression of a solu ble decoy LT beta receptor. This suggests that membrane-bound LT is critica l for NK T cells early in ontogeny, but not for the homeostasis of mature c ells.