title: Role of SLAM in NKT cell development revealed by transgenic complementation in NOD mice.
abstract: Allelic variation of SLAM expression on CD4(+)CD8(+) thymocytes has been proposed to play a major role in NKT cell development. In this article, this hypothesis is tested by the production of subcongenic mouse strains and Slamf1 transgenic lines. The long isoform of the C57BL/6 allele of Slamf1 was transgenically expressed on CD4(+)CD8(+) thymocytes under control of an hCD2 minigene. NOD.Nkrp1b.Tg(Slamf1)1 mice, which had a 2-fold increase in SLAM protein expression on CD4(+)CD8(+) thymocytes, had a 2-fold increase in numbers of thymic NKT cells. The additional thymic NKT cells in NOD.Nkrp1b.Tg(Slamf1)1 mice were relatively immature, with a similar subset distribution to those of congenic NOD.Nkrp1b.Nkt1 and NOD.Nkrp1b.Slamf1 mice, which also express increased levels of SLAM on CD4(+)CD8(+) thymocytes and produce larger numbers of NKT cells. Transgenic enhancement of SLAM expression also increased IL-4 and IL-17 production in response to TCR-mediated stimulation. Paradoxically, NOD.Nkrp1b.Tg(Slamf1)2 mice, which had a 7-fold increase in SLAM expression, showed no significant increase in NKT cells numbers; on the contrary, at high transgene copy number, SLAM expression levels correlated inversely with NKT cell numbers, consistent with a contribution to negative selection. These data confirm a role for SLAM in controlling NKT cell development and are consistent with a role in both positive and negative thymic selection of NKT cells.
authors.affiliation: Comparative Genomics Centre, James Cook University, Townsville, Queensland 4811, Australia.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Jordan
authors.forename: Julie M
authors.initials: JM
authors.lastname: Fletcher
authors.forename: Roby
authors.initials: R
authors.lastname: Jose
authors.forename: Shahead
authors.initials: S
authors.lastname: Chowdhury
authors.forename: Nicole
authors.initials: N
authors.lastname: Gerlach
authors.forename: Janette
authors.initials: J
authors.lastname: Allison
authors.forename: Alan G
authors.initials: AG
authors.lastname: Baxter
mesh_terms: D000818:Animals; D018801:CD2 Antigens / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology*; D002478:Cells, Cultured; D005816:Genetic Complementation Test; D006801:Humans; D051379:Mice; D057507:Mice, 129 Strain; D008805:Mice, Inbred A; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D018801:CD2 Antigens