We have recently demonstrated that synthetic CpG oligonucleotides (ODNs), which function as potent immunostimulators, bind to the multi-lectin receptor DEC-205, resulting in their internalization. DEC-205-deficient mice exhibit impaired dendritic-cell and B-cell maturation, impaired cytokine responses and suboptimal cytotoxic T-cell responses. As murine and human DEC-205 are highly conserved, CpG ODNs destined to clinical applications should be designed to maximize DEC-205 binding.
View Article and Find Full Text PDFSynthetic CpG oligonucleotides (ODN) have potent immunostimulatory properties exploited in clinical vaccine trials. How CpG ODN are captured and delivered to the intracellular receptor TLR9, however, has been elusive. Here we show that DEC-205, a multilectin receptor expressed by a variety of cells, is a receptor for CpG ODN.
View Article and Find Full Text PDFSerpinb9 (Sb9, also called Spi6) is an intracellular inhibitor of granzyme B (GrB) that protects activated cytotoxic lymphocytes from apoptosis. We show here that the CD8(+) subset of splenic dendritic cells (DC), specialized in major histocompatibility complex class I (MHC I) presentation of exogenous antigens (cross-presentation), produce high levels of Sb9. Mice deficient in Sb9 are unable to generate a cytotoxic T-cell response against cell-associated antigen by cross-presentation, but maintain normal MHC-II presentation to helper T cells.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
May 2010
Human blood Vgamma9Vdelta2 T cells respond to signals from microbes and tumors and subsequently differentiate into professional antigen-presenting cells (gammadelta T-APCs) for induction of CD4(+) and CD8(+) T cell responses. gammadelta T-APCs readily take up and degrade exogenous soluble protein for peptide loading on MHC I, in a process termed antigen cross-presentation. The mechanisms underlying antigen cross-presentation are ill-defined, most notably in human dendritic cells (DCs), and no study has addressed this process in gammadelta T-APCs.
View Article and Find Full Text PDFThe skin is constantly exposed to commensal microflora and pathogenic microbes. The stratum corneum of the outermost skin layer employs distinct tools such as harsh growth conditions and numerous antimicrobial peptides (AMPs) to discriminate between beneficial cutaneous microflora and harmful bacteria. How the skin deals with microbes that have gained access to the live part of the skin as a result of microinjuries is ill defined.
View Article and Find Full Text PDFCXCL14 (BRAK) is an ill-described chemokine with unknown receptor selectivity. The human chemokine is constitutively expressed in epithelial tissues and is selective for dendritic cell precursors, indicating a possible function in the maintenance of epithelial DCs. Several studies have addressed the question of human CXCL14 expression in cancerous tissues; however, distribution in healthy tissues and, in particular, the cellular origin of this chemokine has not been thoroughly investigated.
View Article and Find Full Text PDFDendritic cells (DCs) have long been recognized as key regulators of immune responses. However, the process of their recruitment to peripheral tissues and turnover during homeostasis remains largely unknown. The chemokine CXCL14 (BRAK) is constitutively expressed in skin and other epithelial tissues.
View Article and Find Full Text PDFNormal (noninflamed) human skin contains a network of lymphocytes, but little is known about the homing and function of these cells. The majority of alphabeta T cells in normal skin express CCR8 and produce proinflammatory cytokines. In this study we examined other subsets of cutaneous lymphocytes, focusing on those with potential function in purging healthy tissue of transformed and stressed cells.
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