Immunomodulatory dendritic cells in intestinal lamina propria.

The lamina propria (LP) of the small intestine contains many dendritic cells (DC), which are likely to be in close contact with luminal antigens, but their role in intestinal immune responses has been overlooked. Here we show that after feeding mice ovalbumin (OVA), the majority of antigen uptake is associated with DC in the small intestinal LP, and we describe the isolation, purification and initial characterization of theses DC. We obtained >90% CD11c(+) DC using magnetic cell sorting, of which the majority were CD11b(+)CD8alpha(-), with smaller numbers of CD11b(-)CD8alpha(+) and CD11b(-)CD8alpha(-) DC as well as a distinct population of CD11c(int)class II MHC(lo) B220(+) DC.

Oral tolerance: overview and historical perspectives.

Oral tolerance was first detailed almost 100 years ago, and since then, it has been shown repeatedly that feeding a wide variety of nonpathogenic antigens can inhibit subsequent systemic immune responses. All systemic immune responses are susceptible, but the degree and scope of the suppression depends on the nature and dose of the fed antigen. Oral tolerance has been described in most mammals, including humans, and it may be the homeostatic mechanism that prevents hypersensitivity to food antigens, as is found in celiac disease.

The role of dendritic cells in regulating mucosal immunity and tolerance.

The intestinal immune system discriminates between invasive pathogens and antigens that are harmless, such as food proteins and commensal bacteria. The latter groups of antigens normally induce tolerance and a breakdown in this homeostatic process can lead to diseases such as coeliac disease or Crohn's disease. The nature ofthe intestinal immune response depends on how antigen is presented to CD4+ T cells by dendritic cells (DCs).

The role of antigen-presenting cells and interleukin-12 in the priming of antigen-specific CD4+ T cells by immune stimulating complexes.

Immune stimulating complexes (ISCOMs) containing the saponin adjuvant Quil A are vaccine adjuvants that promote a wide range of immune responses in vivo, including delayed-type hypersensitivity (DTH) and the secretion of both T helper 1 (Th1) and Th2 cytokines. However, the antigen-presenting cell (APC) responsible for the induction of these responses has not been characterized. Here we have investigated the role of dendritic cells (DC), macrophages (Mphi) and B cells in the priming of antigen-specific CD4+ T cells in vitro by ISCOMs containing ovalbumin (OVA).

Dendritic cell maturation enhances CD8+ T-cell responses to exogenous antigen via a proteasome-independent mechanism of major histocompatibility complex class I loading.

Immune stimulating complexes (ISCOMS) containing the saponin adjuvant Quil A are vaccine adjuvants that induce a wide range of immune responses in vivo, including strong class I major histocompatibility complex (MHC)-restricted cytotoxic T-lymphocyte activity. However, the antigen-presenting cell responsible for the induction of these responses has not been characterized. Here we have investigated the role of dendritic cells (DC) in the priming of antigen-specific CD8+ T cells in vitro by ISCOMS containing ovalbumin.