Phenotypical and functional differentiation of natural killer cells and T cell receptor γδ cells

The innate or natural immune system provides a rapid and non-specific response against invading pathogens and tumor cells. This first line of defense contains lymphoid cells, such as natural killer (NK) cells and TCR gd cells. In contrast to lymphocytes of the adaptive or acquired immune system, i. e. B lymphocytes and TCR ab cells, major gaps still exist in understanding the maturation, phenotype and function of TCR gd cells and NK cells. The aim of this study was to elaborate the differentiation, phenotype and function of murine NK cells and TCR gd cells. In chapter 1 we focussed on the phenotypical and functional characteristics of murine fetal NK cells. Contrary to NK cells from adult mice, fetal NK cells have a limited NK receptor repertoire. The only NK receptor transcripts that could be detected were Ly49E and CD94/NKG2. In contrast with adult NK cells, fetal NK cells were not able to kill MHC class I-negative target cells, unless fetal NK cells were triggered via an activating NK receptor (part 1). As serological reagents against Ly49E and CD94/NKG2 were lacking, it was not clear whether Ly49E and CD94/NKG2 receptors were expressed at the cell surface of NK cells. Therefore, we generated anti-Ly49E and anti-CD94/NKG2 mAbs (part 2). Using both mAbs in flow cytometry, the phenotype of mouse fetal and adult NK cells was further extended. In part 3, we studied the NK differentiation potential of fetal versus adult hematopoietic precursor cells and analyzed the ordered expression of NK receptors on developing NK cells in vitro and in vivo. In the following chapter, the phenotypic and functional differentiation of gd T cells was studied. In part 1 we studied the intrathymic maturation of human gd T cells, and demonstrate that CD1 is a hallmark to distinguish immature from mature gd thymocytes. In part 2, the generated anti-Ly49E and anti-CD94/NKG2 mAbs have been used to demonstrate the phenotypical and functional relationship between NK cells and one subset of murine TCR gd cells, namely Vg3 T cells. We demonstrate that mature, but not immature, Vg3 T cells express both Ly49E and CD94/NKG2 receptors, and that the cytotoxic activity of Vg3 T cells can be inhibited by the inhibitory CD94/NKG2 receptor. In conclusion we can conclude that this work contributed to a better understanding in the phenotype, function, and differentiation of both NK cells and TCR gd cells