Origin and Development of Human DC Subsets

DCs are continuously produced from hematopoietic stem cells within the bone marrow, and FLT-3 ligand represents the key DC growth and differentiation factor in vivo (Pulendran et al., 2001a). The principal developmental pathways of human DCs from hematopoietic stem cells of the bone marrow are illustrated in Figure 1.1. CD34+ stem cells differentiate into common lymphoid progenitors (CLPs) and common myeloid progenitors (CMPs). CMPs appear to differentiate into CLA+ and CLA- populations, which...

MDCs in Adaptive Immune Responses

Myeloid DC subsets have the capacity to produce IL-12 in response to microbial stimuli and thereby to induce protective Thl-type immune responses however, this capacity may vary with the type of signals delivered to the DC (summarized in Fig. 1.2). Pathogens and or pathogen-derived products such as LPS from Escherichia coli (Pulendran et al., 2001b), peptidoglycan from Gram-positive bacteria (Hilkens et al., 1997), Mycobacterium tuberculosis (Stenger and Modlin, 2002), pertussis toxin (Hou et...

Role of DC Subsets in Adaptive Immunity

The human immune system has evolved to have two distinct mechanisms for protection against microbes. In response to intracellular microbes (bacteria, viruses, fungi, and intracellular parasites), DC subsets produce IL-12 or type I IFN (MDCs and pDCs, respectively), which stimulate CD4+ T helper cells to differentiate into IFN-y-producing T helper (Th) 1 cells (Lanzavecchia and Sallusto, 2001). Th1 cells activate macrophages and CD8+ cytotoxic T cells to kill intracellular microbes. On the other...