The immune system protects us from harmful micro-organisms and tumor cells

immune system, dendritic cells (DCs) are specialized Ag-presenting cells that have a dominant role in the initiation of T cell responses. For this, DCs present intracellular Ags in MHC class I molecules to CD8 T cells or extracellular Ags in MHC class II to CD4 T cells, respectively. Next to these two classical Ag-presentation pathways, DCs are also able to cross-present extracellular Ags in the context of MHC class I to CD8 T cells. This cross-presentation pathway is important for the generation of primary CD8 T cell mediated responses against Ags that are not produced by the presenting DC itself, e.g. cell-specific viruses and tumor cells, which could otherwise not be presented to naive CD8 T cells. DCs form a heterogeneous population in the mouse spleen. Splenic DCs can be subdivided into CD8 and CD8 DC subsets with different phenotype and localization. The specific localization of CD8 DCs in the white pulp and of CD8 DCs in the marginal zone (MZ) is regulated by chemokines, CCR7 and S1P. In spleen, the CD8 DC subset specifically expresses SIRPα, which is a cell surface glycoprotein expressed by myeloid cells that was shown to be involved in migration of several cell types. We showed that in the absence of functional SIRPα in SIRPα-Δ87 mutant mice the number of CD8 DCs in spleen is strongly reduced (chapter 2). Furthermore, SIRPα is involved CD8 DC migration by regulating integrin-mediated cell adhesion. CD8 DCs derived from SIRPα-