Role of the CD8+ dendritic cell subset in transmission of prions.

Controversial results have been observed in mouse models regarding the role of lymphoid tissues in prion pathogenesis. To investigate the role of dendritic cells (DC), we used a transgenic mouse model. In this model (CD11c-N17Rac1), a significant reduction of CD8+ CD11c(hi) DC has been described, and the remaining CD8+ DC demonstrate a reduced capacity for the uptake of apoptotic cells.

CD8alpha+ dendritic cells are required for efficient entry of Listeria monocytogenes into the spleen.

In addition to their bridging function between innate and adaptive immunity, dendritic cells (DCs) may also contribute to primary resistance against infection. Here we analyzed the role of DCs during infection with Listeria monocytogenes by performing systemic in vivo depletion of these cells. We showed that CD8alpha(+) DCs were crucial for L.

Selective Rac1 inhibition in dendritic cells diminishes apoptotic cell uptake and cross-presentation in vivo.

To better understand the influence of cytoskeletal regulation on dendritic cell (DC) function in vivo, the Rho guanosine triphosphatase (GTPase) Rac1 was selectively inhibited in DCs in transgenic (Tg) mice. Although transgene expression did not interfere with the migratory capacities of DC in vivo, a decreased uptake of fluorescent probes was observed. Interestingly, the absence of full Rac1 function most strongly affected the development and function of CD8+ DCs.

Protection from bacterial infection by a single vaccination with replication-deficient mutant herpes simplex virus type 1.

Adaptive immune responses in which CD8(+) T cells recognize pathogen-derived peptides in the context of major histocompatibility complex class I molecules play a major role in the host defense against infection with intracellular pathogens. Cells infected with intracellular bacteria such as Listeria monocytogenes, Salmonella enterica serovar Typhimurium, or Mycobacterium tuberculosis are directly lysed by cytotoxic CD8(+) T cells. For this reason, current vaccines for intracellular pathogens, such as subunit vaccines or viable bacterial vaccines, aim to generate robust cytotoxic T-cell responses.

Selective expression of IL-7 receptor on memory T cells identifies early CD40L-dependent generation of distinct CD8+ memory T cell subsets.

Several recent studies have demonstrated that T-helper cell-dependent events during the initial priming period are required for the generation of CD8(+) T cell-mediated protective immunity. The underlying mechanisms of this phenomenon have not yet been determined, mostly because of difficulties in studying memory T cells or their precursor populations at early stages during immune responses. We identified IL-7 receptor (CD127) surface expression as a marker for long-living memory T cells, most importantly allowing the distinction between memory and effector T cells early after in vivo priming.

Promiscuity of MHC class Ib-restricted T cell responses.

Murine infection with the Gram-positive intracellular bacterium Listeria monocytogenes activates CD8(+) T cells that recognize bacterially derived N-formyl methionine peptides in the context of H2-M3 MHC class Ib molecules. Three peptides, fMIGWII, fMIVIL, and fMIVTLF, are targets of L. monocytogenes-specific CD8(+) T cells.

H2-M3-restricted memory T cells: persistence and activation without expansion.

H2-M3-restricted T cells respond more rapidly to primary Listeria monocytogenes infection than conventional MHC class Ia-restricted T cells. Reinfection with L. monocytogenes, while inducing explosive proliferation of H2-K(d)-restricted T cells, does not stimulate significant expansion of H2-M3-restricted CTL.