Induction of Bordetella pertussis-specific immune memory by DTPa vaccines.

Several vaccines are available against pertussis, differing by the number of Bordetella pertussis antigens that they contain as well as their formulation. The GlaxoSmithKline Biologicals (GSK Bio) tricomponent DTPa vaccine (DTPa3, Infanrix™), and the Sanofi-Pasteur (SP) five-component formulation (DTPa5, Pediacel™) were shown to have comparable short-term efficacy in clinical trials. However, potential differences in long-term protection were recently suggested, which might reflect the elicitation of different specific immune memory by the two vaccines.

AS04, an aluminum salt- and TLR4 agonist-based adjuvant system, induces a transient localized innate immune response leading to enhanced adaptive immunity.

Adjuvant System 04 (AS04) combines the TLR4 agonist MPL (3-O-desacyl-4'-monophosphoryl lipid A) and aluminum salt. It is a new generation TLR-based adjuvant licensed for use in human vaccines. One of these vaccines, the human papillomavirus (HPV) vaccine Cervarix, is used in this study to elucidate the mechanism of action of AS04 in human cells and in mice.

Characterization of a subset of antigen-specific human central memory CD4+ T lymphocytes producing effector cytokines.

CCR7(+ )central memory (T(CM)) CD4(+) T cells play a central role in long-term immunological memory. Recent reports indicate that a proportion of CD4(+) T(CM) is able to produce effector cytokines. The phenotype and the role of this subset remain unknown.

Antigen-specific central memory CD4+ T lymphocytes produce multiple cytokines and proliferate in vivo in humans.

The function of Ag-specific central (T(CM)) and effector (T(EM)) memory CD4+ T lymphocytes remains poorly characterized in vivo in humans. Using CD154 as a marker of Ag-specific CD4+T cells, we studied the differentiation of memory subsets following anti-hepatitis B immunization. Hepatitis B surface Ag (HBs)-specific memory CD4+T cells were heterogeneous and included T(CM) (CCR7+CD27+) and T(EM) (CCR7(-)CD27(+/-)).

Distinct mechanisms are involved in tumoristatic and tumoricidal activities of monocyte-derived dendritic cells.

Monocyte-derived dendritic cells (DC) were found to inhibit proliferation of different tumor cell lines. LPS-induced maturation of DC strongly increased their capacity to inhibit tumor cell growth. We observed that tumoristatic activity of LPS-activated DC was independent of their cytotoxic potential.

Tumoricidal activity of monocyte-derived dendritic cells: evidence for a caspase-8-dependent, Fas-associated death domain-independent mechanism.

Monocyte-derived dendritic cells (DC) were found to be cytotoxic for several tumor cell lines including Jurkat cells, which were killed through a calcium-independent pathway. K562 cells were resistant, excluding a NK cell-like activity. DC-mediated apoptosis did not involve classical death receptors because it was not reversed by blocking TNF/TNFR, CD95/CD95 ligand, or TNF-related apoptosis-inducing ligand/TNF-related apoptosis-inducing ligand receptor interactions.

[Anti-tumor immunotherapy based on dendritic cells].

In cancer immunotherapy, the use of dendritic cells (DC) loaded with tumor-associated antigens (TAA) emerged as a promising strategy. We initiated 3 pilot clinical trials with immunological endpoints using TAA loaded autologous DC. These trials showed that this approach was safe and associated with the induction of potent TAA specific IFN-gamma responses, which were transient despite the providing a further help through KLH presentation.

Expression of c-FLIP(L) and resistance to CD95-mediated apoptosis of monocyte-derived dendritic cells: inhibition by bisindolylmaleimide.

To gain insight into the mechanisms controlling apoptosis of dendritic cells (DC), human monocyte-derived DC were analyzed for their expression of CD95 (Fas/Apo-1) and their response to CD95 ligation. Although DC expressed the CD95 molecule on their membrane, they did not undergo apoptosis on CD95 ligation unless sensitized by cycloheximide. In parallel, DC synthesized c-FLIP(L), an inhibitor of the CD95-mediated death-signaling cascade.

Trypanosoma cruzi infects human dendritic cells and prevents their maturation: inhibition of cytokines, HLA-DR, and costimulatory molecules.

Trypanosoma cruzi, a parasitic protozoan, is the etiological agent of Chagas' disease. Despite the many immune system disorders recognized in this infection and the crucial role played by dendritic cells (DC) in acquired immune responses, it was not known whether these cells could be infected by T. cruzi trypomastigotes and the consequences of such an infection on their immune functions.

Inhibition of human dendritic cell functions by methylprednisolone.

Background: The aim of this study was to better define how glucocorticoids influence primary human T cell responses. Dendritic cells (DC*) are the most effective antigen presenting cells able to activate naive T cells. Previous studies have shown that dexamethasone impaired the function of murine DC.

N-acetyl-L-cysteine inhibits primary human T cell responses at the dendritic cell level: association with NF-kappaB inhibition.

N-acetyl-L-cysteine (NAC) is an antioxidant molecule endowed with immunomodulatory properties. To investigate the effect of NAC on the induction phase of T cell responses, we analyzed its action on human dendritic cells (DC) derived from adherent PBMC cultured with IL-4 and granulocyte-macrophage CSF. We first found that NAC inhibited the constitutive as well as the LPS-induced activity of the transcription factor NF-kappaB.