Natural killer cells activated by MHC class I(low) targets prime dendritic cells to induce protective CD8 T cell responses.

Conserved molecular patterns derived from pathogenic microorganisms prime antigen-presenting dendritic cells (DC) to induce adaptive T cell responses. In contrast, virus-infected or tumor cells that express low levels of major histocompatibility complex (MHC) class I activate natural killer (NK) cells for direct killing. It is unknown whether NK cell recognition of MHC class I(low) targets can also induce adaptive T cell responses.

IL-4 instructs TH1 responses and resistance to Leishmania major in susceptible BALB/c mice.

Immunity to infection with intracellular pathogens is regulated by interleukin 12 (IL-12), which mediates protective T helper type 1 (TH1) responses, or IL-4, which induces TH2 cells and susceptibility. Paradoxically, we show here that when present during the initial activation of dendritic cells (DCs) by infectious agents, IL-4 instructed DCs to produce IL-12 and promote TH1 development. This TH1 response established resistance to Leishmania major in susceptible BALB/c mice.

Analysis of catabolite control protein A-dependent repression in Staphylococcus xylosus by a genomic reporter gene system.

A single-copy reporter system for Staphylococcus xylosus has been developed, that uses a promoterless version of the endogenous beta-galactosidase gene lacH as a reporter gene and that allows integration of promoters cloned in front of lacH into the lactose utilization gene cluster by homologous recombination. The system was applied to analyze carbon catabolite repression of S. xylosus promoters by the catabolite control protein CcpA.

Eradication of disseminated lymphomas with CpG-DNA activated T helper type 1 cells from nontransgenic mice.

Various evidence suggests that adoptive transfer of polyclonal, tumor-specific, IFN-gamma-producing CD4+ T cells [T helper type 1 (Th1) cells] should be highly efficient for tumor immune therapy. However, this approach could not be tested because very few MHC class II-restricted tumor peptides have been defined. Here we show that stimulation of freshly isolated T helper cells with syngeneic tumor cells and antigen-presenting cells in the presence of immunostimulatory CpG DNA allows the generation of large numbers of strongly polarized, tumor-specific Th1 cells within 3 weeks of culture, even when T helper cells were derived from tumor-bearing mice.

CpG oligodeoxynucleotides trigger protective and curative Th1 responses in lethal murine leishmaniasis.

Synthetic oligodeoxynucleotides containing CpG dinucleotides (CpG-ODN) mimic the immunostimulatory qualities of bacterial DNA. We asked whether immunostimulation by CpG-ODN predisposes for a commitment toward a Th1 vs a Th2 response in Leishmania major infection, a model for a lethal Th2-driven disease, in BALB/c mice. CpG-ODN induced Th1 effector T cells in vitro and conveyed protective immunity to disease-prone BALB/c mice in vivo.