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 expressi ng the H-2D(d) gene under the control of the mouse metallothionein-I promot er. 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 admi nistration resulted in a 1.5- and 8.5-fold increase in H-2D(d) expression i n 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 M TD mice, even in the absence of mine. 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 r eveal a difference between T cells and NK cells in their requirements for M HC class I molecules in specificity development.