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Division of Developmental Immunology and
Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121
The development of lymphoid organs requires membrane-bound
lymphotoxin (LT), a heterotrimer containing LT
and LTß, but the
effects of LT on T cell function have not been characterized
extensively. Upon TCR cross-linking in vitro, splenocytes from both
LT-/- and
LTß-/- mice failed to produce IL-4 and
IL-10 due to a reduction in NK T cells. Concordantly,
LT-/- and
LTß-/- mice did not respond to the
lipoglycan -galactosylceramide, which is presented by mouse CD1 to
V14+ NK T cells. Interestingly, both populations of NK T
cells, including those that are mouse CD1 dependent and
-galactosylceramide reactive and those that are not, were affected
by disruption of the LT and LTß 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 LTß
receptor. This suggests that membrane-bound LT is critical for NK T
cells early in ontogeny, but not for the homeostasis of mature
cells.
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