scholarly journals Downregulation of the antigen presenting cell function(s) of pulmonary dendritic cells in vivo by resident alveolar macrophages.

1993 ◽  
Vol 177 (2) ◽  
pp. 397-407 ◽  
Author(s):  
P G Holt ◽  
J Oliver ◽  
N Bilyk ◽  
C McMenamin ◽  
P G McMenamin ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Alveolar Macrophages ◽  
Cell Function ◽  
Normal Lung ◽  
Antigen Presenting Cell ◽  
Epithelial Surface ◽  
Intratracheal Administration ◽  
Antigen Presenting

Class II major histocompatibility complex (Ia)-bearing dendritic cells (DC) from airway epithelium and lung parenchyma express low-moderate antigen presenting cell (APC) activity when freshly isolated. However, this function is markedly upregulated during overnight culture in a manner analogous to epidermal Langerhans cells. The in vitro "maturation" process is inhibited by coculture with pulmonary alveolar macrophages (PAM) across a semipermeable membrane, and the degree of inhibition achieved can be markedly increased by the presence of tumor necrosis factor alpha. In addition, PAM-mediated suppression of DC function is abrogated via inhibition of the nitric oxide synthetase pathway. Functional maturation of the DC is accompanied by increased expression of surface Ia, which is also inhibited in the presence of PAM. Prior elimination of PAM from DC donors via intratracheal administration of the cytotoxic drug dichloromethylene diphosphonate in liposomes, 24-72 h before lung DC preparation, achieves a comparable upregulation of APC activity, suggesting that (consistent with the in vitro data) the resident PAM population actively suppresses the APC function of lung DC in situ. In support of the feasibility of such a regulatory mechanism, electron microscopic examination of normal lung fixed by intravascular perfusion in the inflated state (which optimally preserves PAM in situ), revealed that the majority are preferentially localized in recesses at the alveolar septal junctions. In this position, the PAM are in intimate association with the alveolar epithelial surface, and are effectively separated by as little as 0.2 microns from underlying interstitial spaces which contain the peripheral lung DC population. A similar juxtaposition of airway intraepithelial DC is demonstrated with underlying submucosal tissue macrophages, where the separation between the two cell populations is effectively the width of the basal lamina.

scholarly journals Pros and Cons of Antigen-Presenting Cell Targeted Tumor Vaccines

2015 ◽  
Vol 2015 ◽  
pp. 1-18 ◽  
Author(s):  
Cleo Goyvaerts ◽  
Karine Breckpot
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Potential Benefit ◽  
Tumor Vaccines ◽  
Antigen Presenting Cell ◽  
Leading Role ◽  
True Meaning ◽  
Pros And Cons ◽  
Antigen Presenting

In therapeutic antitumor vaccination, dendritic cells play the leading role since they decide if, how, when, and where a potent antitumor immune response will take place. Since the disentanglement of the complexity and merit of different antigen-presenting cell subtypes, antitumor immunotherapeutic research started to investigate the potential benefit of targeting these subtypesin situ. This review will discuss which antigen-presenting cell subtypes are at play and how they have been targeted and finally question the true meaning of targeting antitumor-based vaccines.

Enhancement of the Antigen-Presenting Cell Function of Mantle Cell Lymphomas (MCL) by Novel Molecularly Based Immunotherapeutic Strategies.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2315-2315
Author(s):  
Hongwei Wang ◽  
Fengdong Cheng ◽  
D. Noyes ◽  
K. Wright ◽  
S. Mohapatra ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Histone Deacetylases ◽  
Cell Function ◽  
Antigen Presenting Cell ◽  
Ifn Gamma ◽  
Stat3 Signaling ◽  
Antigen Presenting ◽  
In Vitro Treatment

Abstract MCL is an aggressive and incurable B-cell malignancy with an intrinsic characteristic to relapse after an initial good response to treatment. Manipulation of the immune system to unleash its well-known specificity and long-lasting protective effect might provide a unique opportunity to induce more durable responses in MCL. In previous studies in an A20 B-cell lymphoma murine model we have demonstrated that augmentation of the antigen-presenting cell function of the malignant B-cell is required for elicitation of an effective anti-lymphoma immunity1. Inhibition of Stat3 signaling, a negative regulator of inflammatory responses, and modulation of histone deacetylases function were identified as two novel targets to augment the immunogenicity of the malignant B-cell. In this study we determined therefore whether manipulation of these intracellular pathways in murine and human MCL cells could result in priming of antigen-specific T-cells and/or restoration of the responsiveness of tolerant T-cells. First, in vitro treatment of FC-muMCL1 cells - cell line derived from a MCL tumor that arise following pristine injection into Em-cyclin D1 transgenic mice- with increasing concentrations of the Stat3 inhibitors, Cucurbitacin I (CuI) or CPA-7 resulted in an enhanced presentation of OVA-peptide to naive CD4+ T-cells specific for a MHC class II restricted epitope of Ovalbumin (OT-II cells). Indeed, these antigen-specific T-cells produce higher levels of IL-2 and IFN-gamma compared to anti-OVA T cells that encountered cognate antigen in FC-muMCL1 cells treated with LPS alone. Similarly, we found that culture of the human MCL cells JEKO or Z138 with allogeneic human peripheral blood mononuclear cells in the presence of increasing concentrations of the Stat3 inhibitors also resulted in increased IL-2 production by T-cells. In the next set of experiments, we determined whether treatment of FC-muMCL1 cells with the hydroxamic acid analogue pan-HDAC inhibitor LAQ824 could influence their antigen-presenting capabilities and their ability to activate T-cell responses. Unlike, MCL cells treated with LPS alone, FC-muMCL1 cells treated with LPS and LAQ824 effectively prime antigen-specific CD4+ T-cells as determined by their production of both IL-2 and IFN-gamma in response to cognate peptide. Furthermore, in vitro treatment of Z138 MCL cells with LAQ824 also led to enhanced IFN-gamma production by allogeneic human PBMCs. Taken together, our findings points to inhibition of Stat3 signaling and inhibition of histone deacetylases as appealing molecularly based immunotherapeutic strategies to augment the immunogenicity of MCL cells.

scholarly journals Dendritic cells pulsed with protein antigens in vitro can prime antigen-specific, MHC-restricted T cells in situ.

1990 ◽  
Vol 172 (2) ◽  
pp. 631-640 ◽  
Author(s):  
K Inaba ◽  
J P Metlay ◽  
M T Crowley ◽  
R M Steinman
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell Response ◽  
Foreign Protein ◽  
Protein Antigens ◽  
Mhc Molecules ◽  
Antigen Presenting ◽  
Vacuolar System

T cells recognize peptides that are bound to MHC molecules on the surface of different types of antigen-presenting cells (APC). Antigen presentation most often is studied using T cells that have undergone priming in situ, or cell lines that have been chronically stimulated in vitro. The use of primed cells provides sufficient numbers of antigen-reactive lymphocytes for experimental study. A more complete understanding of immunogenicity, however, requires that one develop systems for studying the onset of a T cell response from unprimed lymphocytes, especially in situ. Here it is shown that mouse T cells can be reliably primed in situ using dendritic cells as APC. The dendritic cells were isolated from spleen, pulsed with protein antigens, and then administered to naive mice. Antigen-responsive T cells developed in the draining lymphoid tissue, and these T cells only recognized protein when presented on cells bearing the same MHC products as the original priming dendritic cells. In contrast, little or no priming was seen if antigen-pulsed spleen cells or peritoneal cells were injected. Since very small amounts of the foreign protein were visualized within endocytic vacuoles of antigen-pulsed dendritic cells, it is suggested that dendritic cells have a small but relevant vacuolar system for presenting antigens over a several day period in situ.

Antigen-presenting cell function of dendritic cells and macrophages in proliferative T cell responses to soluble and particulate antigens

1986 ◽  
Vol 16 (4) ◽  
pp. 345-350 ◽  
Author(s):  
Martien L. Kapsenberg ◽  
Marcel B. M. Teunissen ◽  
Frank E. M. Stiekema ◽  
Hiskias G. Keizer
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Cell Function ◽  
T Cell Responses ◽  
Antigen Presenting Cell ◽  
Cell Responses ◽  
Antigen Presenting

Isolation of Human Blood Dendritic Cells Using the CMRF-44 Monoclonal Antibody: Implications for Studies on Antigen-Presenting Cell Function and Immunotherapy

Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3708-3716 ◽  
Author(s):  
D.B. Fearnley ◽  
A.D. McLellan ◽  
S.I. Mannering ◽  
B.D. Hock ◽  
D.N.J. Hart
Keyword(s):  
Monoclonal Antibody ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Cell Function ◽  
Cell Clone ◽  
Antigen Uptake ◽  
T Cell Clone ◽  
Antigen Presenting ◽  
Dc Maturation

Abstract Dendritic cells (DC) are potent antigen-presenting cells (APC) with the capacity to stimulate a primary T lymphocyte immune response and are therefore of interest for potential immunotherapeutic applications. Freshly isolated DC or DC precursors may be preferable for studies of antigen uptake and the potential control of APC costimulator activity. In this report, we report that the monoclonal antibody CMRF-44 can be used to detect early DC differentiation. The majority of DC circulating in blood do not express any known DC lineage specific markers, but can be identified by CMRF-44 labeling after a brief period of in vitro culture. The sequential acquisition of DC activation antigens allows the identification of two stages of DC maturation/activation. Cytokines, especially granulocyte-macrophage colony-stimulating factor (GM-CSF ) and tumor necrosis factor (TNF )α, enhance both phases of this process, whereas CD40-ligand trimer preferentially enhances the final DC maturation to a fully mature, activated phenotype. DC positively selected using CMRF-44 possess potent allostimulatory activity and are efficient at the uptake, processing, and presentation of soluble antigens for both primary and secondary immune responses. CMRF-44+ DC are also more potent than other APC types at restimulation of a chronic myeloid leukemia peptide specific T-cell clone. The use of a purified population of freshly isolated DC may be advantageous in attempts to initiate, maintain, and direct immune responses for immunotherapeutic applications.

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