Membrane lymphotoxin is required for the development of different subpopulations of NK T cells |
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Authors: | Elewaut D Brossay L Santee S M Naidenko O V Burdin N De Winter H Matsuda J Ware C F Cheroutre H Kronenberg M |
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Affiliation: | Division of Developmental Immunology and Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA. |
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Abstract: | The development of lymphoid organs requires membrane-bound lymphotoxin (LT), a heterotrimer containing LTalpha and LTbeta, but the effects of LT on T cell function have not been characterized extensively. Upon TCR cross-linking in vitro, splenocytes from both LTalpha-/- and LTbeta-/- mice failed to produce IL-4 and IL-10 due to a reduction in NK T cells. Concordantly, LTalpha-/- and LTbeta-/- mice did not respond to the lipoglycan alpha-galactosylceramide, which is presented by mouse CD1 to Valpha14+ 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 LTalpha and LTbeta 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 LTbeta 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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