title: B6 strain Ly49I inhibitory gene expression on T cells in FVB.Ly49IB6 transgenic mice fails to prevent normal T cell functions.
abstract: Inhibitory Ly49 receptors expressed on NK cells provide a mechanism for tolerance to normal self tissues. The immunoregulatory tyrosine-based inhibitory motifs present in some Ly49s are able to transmit an inhibitory signal upon ligation by MHC class I ligands. In our system, as well as others, mice transgenic for inhibitory Ly49 receptors express these receptors on both NK and T cells. FVB (H2(q)) mice transgenic for the B6 strain Ly49I (Ly49I(B6)) express the inhibitory Ly49 receptor on the surface of both T and NK cells. Although Ly49I functions to prevent NK-mediated rejection of H2(b) donor bone marrow cells in this transgenic mouse strain, the T cells do not appear to be affected by the expression of the Ly49I transgene. FVB.Ly49I T cells have normal proliferative capabilities both in vitro and in vivo in response to the Ly49I ligand, H2(b). In vivo functional T cell assays were also done, showing that transgenic T cells were not functionally affected. T cells in these mice also appear to undergo normal T cell development and activation. Only upon stimulation with suboptimal doses of anti-CD3 in the presence of anti-Ly49I is T cell proliferation inhibited. These data are in contrast with findings in Ly49A, and Ly49G2 receptor transgenic models. Perhaps Ly49I-H2(b) interactions are weaker or of lower avidity than Ly49A-H-2D(d) interactions, especially in T cells.
authors.affiliation: Department of Pathology, Laboratory of Molecular Pathology, and Graduate Program in Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Morris
authors.forename: Jingxuan
authors.initials: J
authors.lastname: Liu
authors.forename: Veera
authors.initials: V
authors.lastname: Arora
authors.forename: Thaddeus C
authors.initials: TC
authors.lastname: George
authors.forename: Jennifer
authors.initials: J
authors.lastname: Klem
authors.forename: John D
authors.initials: JD
authors.lastname: Schatzle
authors.forename: Vinay
authors.initials: V
authors.lastname: Kumar
authors.forename: Michael
authors.initials: M
authors.lastname: Bennett
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis* / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D007156:Immunologic Memory / Q000235:genetics; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics*; D013491:Suppressor Factors, Immunologic / Q000096:biosynthesis* / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D019076:Transgenes / Q000276:immunology*
chemical_list: D000950:Antigens, Ly; C408248:Ly49I antigen; D011971:Receptors, Immunologic; D013491:Suppressor Factors, Immunologic