Differential effects on T cell and NK cell development by tissue-specific expression of H-2D(d) transgene.
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.
Johansson
M H
MH
Microbiology and Tumor Biology Center (MTC), Karolinska Institute, Stockholm, Sweden.
Bieberich
C
C
Kâse-Sjöström
A
A
Yoshioka
T
T
Höglund
E
E
Christy
B A
BA
Scangos
G
G
Kärre
K
K
Jay
G
G
Höglund
P
P
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*
D006183:H-2 Antigens