Adaptation to replating of dendritic cells synergizes with Toll-like receptor stimuli and enhances the pro-inflammatory cytokine profile.

Background: As initiators of the adaptive immune response, dendritic cells (DCs) can be used for anti-cancer immunotherapy. On addition of proper maturation stimuli DCs mature and produce pro-inflammatory cytokines that skew T cells in the direction needed for anti-cancer therapy. Further optimization of DC maturation might improve the efficacy of DCs for clinical application.

Comparison of media and serum supplementation for generation of monophosphoryl lipid A/interferon-γ-matured type I dendritic cells for immunotherapy.

Background Aims: Ex vivo-generated monocyte-derived dendritic cells (DCs) matured with monophosphoryl lipid A (MPLA) and interferon-γ (IFN-γ) can be used as cancer immunotherapy. MPLA/IFN-γ DCs induce Th1 T cell responses and have migratory capacity. Different culture regimens have been used for generation of immunotherapeutic DCs, with varying results.

TLR4-mediated pro-inflammatory dendritic cell differentiation in humans requires the combined action of MyD88 and TRIF.

TLR4 ligation can activate both the MyD88 and the Toll-IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF) signaling route. Whereas MyD88 is generally recognized as a universal adaptor for pro-inflammatory responses, TRIF is mainly thought to contribute to specific type I IFN responses. Here, we investigated the contribution of both MyD88 and TRIF to TLR4-mediated pro-inflammatory dendritic cell (DC) differentiation in human.

Direct ex vivo detection of HLA-DR3-restricted cytomegalovirus- and Mycobacterium tuberculosis-specific CD4+ T cells.

In order to detect epitope-specific CD4+ T cells in mycobacterial or viral infections in the context of human class II major histocompatibility complex protein human leukocyte antigen (HLA)-DR3, two HLA-DR3 tetrameric molecules were successfully produced. One contained an immunodominant HLA-DR3-restricted T-cell epitope derived from the 65-kDa heat-shock protein of Mycobacterium tuberculosis, peptide 1-13. For the other tetramer, we used an HLA-DR3-restricted T-cell epitope derived from cytomegalovirus (CMV) pp65 lower matrix protein, peptide 510-522, which induced high levels of interferon (IFN)-gamma-producing CD4+ T cells in three of four HLA-DR3-positive CMV-seropositive individuals up to 0.

Expression of the murine CD27 ligand CD70 in vitro and in vivo.

The interaction between TNFR family member CD27 and its ligand CD70 promotes lymphocyte expansion and effector cell formation. In humans, control of CD27 function is partly regulated by the restricted expression of CD70. We used newly developed mAbs to characterize murine (m) CD70 expression in vitro and in vivo.

Lethal T cell immunodeficiency induced by chronic costimulation via CD27-CD70 interactions.

It has been proposed that HIV-1, in addition to directly infecting and killing CD4+ T cells, causes T cell dysfunction and T cell loss by chronic immune activation. We analyzed the effects of chronic immune activation in mice that constitutively expressed CD70, the ligand for the tumor necrosis factor receptor family member CD27, on B cells. CD70 transgenic (CD70 Tg) mice showed a progressive conversion of naive T cells into effector-memory cells, which culminated in the depletion of naive T cells from lymph nodes and spleen.