title: Differential effects on T cell and NK cell development by tissue-specific expression of H-2D(d) transgene.
abstract: The effect of tissue-specific expression of the MHC class I molecule H-2D(d) on T cell and NK cell specificity was studied in transgenic mice expressing the H-2D(d) gene under the control of the mouse metallothionein-I promoter. MTD mice expressed high amounts of H-2D(d) in the liver, intestine and testis, but only minute amounts in the thymus, spleen and kidney. Zinc administration resulted in a 1.5- and 8.5-fold increase in H-2D(d) expression in the liver and the intestine, respectively, but did not affect expression in the other organs tested. T cell tolerance developed towards H-2D(d) in MTD mice, even in the absence of zinc. In contrast, NK cell-mediated natural resistance against lymphoma grafts was not seen in MTD mice, despite zinc administration. NK cells in MTD mice also failed to develop self tolerance to H-2D(d). The lack of functional effects did not result from inability of NK cells in MTD mice to interact with H-2D(d), as down-regulation of Ly49A receptor expression was observed on liver NK cells in MTD mice. Our data reveal a difference between T cells and NK cells in their requirements for MHC class I molecules in specificity development.
authors.affiliation: Microbiology and Tumor Biology Center (MTC), Karolinska Institute, Stockholm, Sweden.
authors.forename: M H
authors.initials: MH
authors.lastname: Johansson
authors.forename: C
authors.initials: C
authors.lastname: Bieberich
authors.forename: A
authors.initials: A
authors.lastname: Kâse-Sjöström
authors.forename: T
authors.initials: T
authors.lastname: Yoshioka
authors.forename: E
authors.initials: E
authors.lastname: Höglund
authors.forename: B A
authors.initials: BA
authors.lastname: Christy
authors.forename: G
authors.initials: G
authors.lastname: Scangos
authors.forename: K
authors.initials: K
authors.lastname: Kärre
authors.forename: G
authors.initials: G
authors.lastname: Jay
authors.forename: P
authors.initials: P
authors.lastname: Höglund
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D006183:H-2 Antigens