Failure and Success in Abolition of Virus‐Specific CTL‐Response Defects by Dendritic Cells

Kast, W. Martin; Boog, Claire J. P.; Roep, Bart O.; Voordouw, A. C.; Melief, C. J. M.

doi:10.1111/j.1749-6632.1988.tb36359.x

Cited by 27 publications

(42 citation statements)

References 7 publications

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“…Dendritic cells are extremely potent antigen presenting cells, which can even restore MHC linked antigen specific and virus specific cytotoxic T cell response defects (Boog et al, 1985Kast et al, 1988). The laborious standard isola tion procedure of D C (Steinman et al, 1979) takes 2 days and may lead to the activation of these cells through adhesion to tissue culture plates.…”

Section: Discussionmentioning

confidence: 99%

“…Spleen cells from in vivo primed mice were depleted of B cells and adherent cells (APC) by a double pas sage through Sephadex G-10 columns (Pharmacia Fine Chemicals, Uppsala, Sweden) (Ly et al, 1974) followed by a nylonwool passage (Scrubbed Nylon Fiber, Ferwall Laboratories, Deerfield, IL, USA) as described by Kast et al, (1988). FACS analysis showed that the responder cells con tained > 70% T cells (data not shown).…”

Section: Apc Activity O F the Ce Fractionsmentioning

confidence: 99%

“…After 5 days culture at 37°C in humified air with 5% C 0 2, cells were harvested by density centrifugation on Lympholyte M (Cedarlane Laboratories). Viable cells were washed twice and used as effector cells in a cell mediated cytotoxicity assay as described by 105 Kast et al (1988). In brief, various numbers of effector cells and 2 X 103 N a2-51C r0 4 (5ICr)-labeled target cells were incubated for 6 h in 100 ¡11 culture medium in 96 well U bottomed plates (Costar).…”

Section: Primary Responsementioning

confidence: 99%

“…DC can be distinguished from other antigen presenting cells by their excellent APC activity as illustrated by their capacity to present Sendai virus (Kast et al, 1988). To determine which CE fraction has the highest APC activity on a per cell basis, irradiated, Sendai virus-infected cells of each CE fraction were used as stimulator cells in a secondary Sendai virus-specific T cell prolifera tion assay using a responder/stim ulator ratio of 2:1, 6:1 and 12:1 (Fig.…”

Section: A Pc Activity O F the Ce Fractionsmentioning

confidence: 99%

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A rapid isolation procedure for dendritic cells from mouse spleen by centrifugal elutriation

Ossevoort

Toes

Bruijn

et al. 1992

Journal of Immunological Methods

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The standard isolation procedure for antigen presenting dendritic cells (DC) takes 2 days and includes selective adherence to tissue culture plates which may lead to the activation of these cells. This report describes the isolation of DC by centrifugal elutriation (CE). Murine spleen cells were separated on the basis of size and density into 7 CE fractions. This method took 90 min. Ceils from each CE fraction were characterized by fluorescence activated cell sorter (FACS) analysis and their antigen presenting cell (APC) activity was determined by a secondary Sendai virus specific T cell proliferation assay. CE fraction 5 contained most of the DC with a concentration of 6-10% , representing an approximately 15-fold enrichment compared to unseparated spleen cells ( < 1 % DC). This CE fraction also exhibited the highest APC activity, which was almost completely abolished after depletion of DC by treatment with monoclonal antibody 33D1 (DC-marker) and complement. Further enrichment of CE fraction 5 by discontinuous density gradient centrifugation resulted in a cell population containing 35-55% 33Dl-positive cells with similar characteristics as DC isolated by the standard procedure, such as the capacity to induce a primary viral peptide specific CTL response. Two-color FACS analysis showed an increase in MHC expression on 33Dl-positive cells of CE fraction 5 after 18 h culture involving cell adhesion to a similar level as the M HC expression on DC isolated by the standard procedure. During this same period their morphology changed from a round to a dendritic appearance. In conclusion, our results indicate that CE is well suited for isolating DC more rapidly and without activation of these cells by adherence, a process which readily occurs in the standard isolation procedure.

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Section: Discussionmentioning

confidence: 99%

Section: Apc Activity O F the Ce Fractionsmentioning

confidence: 99%

Section: Primary Responsementioning

confidence: 99%

Section: A Pc Activity O F the Ce Fractionsmentioning

confidence: 99%

See 2 more Smart Citations

A rapid isolation procedure for dendritic cells from mouse spleen by centrifugal elutriation

Ossevoort

Toes

Bruijn

et al. 1992

Journal of Immunological Methods

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“…Reactivation of the latent virus leads again to lytic replication, accompanied by the typical herpes lesions (Daheshia et al, 1998;Whitley & Roizman, 2001). Although DCs are able to stimulate protective antiviral immune responses (Ludewig et al, 1998) and are well-known as the most effective mediators of cytotoxic T-lymphocyte (CTL) responses to influenza virus (Nonacs et al, 1992), Sendai virus, Moloney murine leukemia virus (Kast et al, 1988) and HSV (Hengel et al, 1987) in the murine model, in the case of HSV-1, the immune system fails to eliminate the virus particles generated during the acute stage, which leads in consequence to the establishment of a persistent infection (Becker, 2002(Becker, , 2003Whitley & Roizman, 2001 For HSV-1, several mechanisms that suppress a specific immune response have been identified (Pollara et al, 2004a): the immediate-early gene product ICP47 has been characterized to interfere with the transporter associated with antigen presentation (TAP) and inhibits the transport of peptides into the endoplasmic reticulum (Ahn et al, 1996;Goldsmith et al, 1998;Hill et al, 1995). Furthermore, infection of mature DCs with HSV-1 leads to a significant downregulation of CD83 surface expression, resulting in a reduced capacity to stimulate T cell-mediated immunity (Kruse et al, 2000).…”

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confidence: 99%

Infection of mature dendritic cells with herpes simplex virus type 1 dramatically reduces lymphoid chemokine-mediated migration

Prechtel

Turza

Kobelt

et al. 2005

Journal of General Virology

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Herpes simplex virus type 1 (HSV-1) is able to establish latency in infected individuals. In order to characterize potential new immune-escape mechanisms, mature dendritic cells (DCs) were infected with HSV-1 and total cellular RNA was isolated from infected and mock-infected populations at different time points. RNA profiling on Affymetrix Human Genome U133A arrays demonstrated a dramatic downregulation of the migration-mediating surface molecules CCR7 and CXCR4, an observation that was further confirmed by RT-PCR and fluorescence-activated cell sorting analyses. Furthermore, migration assays revealed that, upon infection of mature DCs, CCR7-and CXCR4-mediated migration towards the corresponding CCL19 and CXCL12 chemokine gradients was strongly reduced. It is noteworthy that the infection of immature DCs with HSV-1 prior to maturation led to a failure of CCR7 and CXCR4 upregulation during DC maturation and, as a consequence, also induced a block in their migratory capacity. Additional migration assays with a Dvhs mutant virus lacking the virion host shutoff (vhs) gene, which is known to degrade cellular mRNAs, suggested a vhs-independent mechanism. These results indicate that HSV-1-infected mature DCs are limited in their capacity to migrate to secondary lymphoid organs, the areas of antigen presentation and T-cell stimulation, thus inhibiting an antiviral immune response. This represents a novel, previously unrecognized mechanism for HSV-1 to escape the human immune system. INTRODUCTIONDendritic cells (DCs) are bone marrow-derived leukocytes and represent the best-known group of antigen-presenting cells (APCs) today. In order to induce specific T cellmediated immune responses, they act as the sentinels of the immune system and lie in wait in an immature state in almost all peripheral tissues (Banchereau & Steinman, 1998). Maturation is induced by contact of immature DCs with various products of infectious agents (Aliprantis et al., 1999;Brightbill et al., 1999;Cella et al., 1999). During maturation, DCs lose their ability to take up antigens and migrate from the sites of antigen accumulation to the areas of antigen presentation, primarily the T-cell zones of the secondary lymphoid organs (Banchereau & Steinman, 1998;Ridge et al., 1998).Immature DCs differ significantly from mature DCs in their response to specific chemokines, their ability to migrate and their capacity to stimulate immune responses (Gunn, 2003). Whilst immature DCs respond to many CC and CXC chemokines, such as CCL3 (MIP-1a), CCL4 (MIP-1b), CCL5 (RANTES) and CCL20 (MIP-3a), the expression or activity of the corresponding receptors is reduced or abolished completely in mature DCs 1998). As a consequence of the enhanced expression of CCR7 and CXCR4, mature DCs show an increased response to CCL19 (MIP-3b) and CXCL12 (SDF-1a) (Cavanagh & Von Andrian, 2002; Delgado et al., 1998; Förster et al., 1999;Gunn et al., 1999). The necessity of CCR7 expression for the induction of a primary immune response (Förster et al., 1999;Parlato et al., 2001) has ...

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Specific immune responses restored by alteration in carbohydrate chains of surface molecules on antigen‐presenting cells

et al. 1989

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Two class I major histocompatibility (MHC) mutant mouse strains, H-2bm14 and H-2bm6, differ from the strain of origin C57BL/6 (B6, H-2b) in one and two amino acids of the H-2Db and H-2Kb molecule, respectively. The bm14 Db mutation results in specific failure of female bm14 mice to generate a cytotoxic T lymphocyte (Tc) response to the male-specific antigen H-Y. The allospecific Tc response of CD8+ B6T cells against bm6 Kb mutant spleen cells, in contrast to that against other Kb mutants, is absolutely CD4+ T helper cell dependent. Purified CD8+ T cells completely fail to respond. We now report that the inability to mount these specific immune responses is restored by the use of dendritic cells (DC) as antigen-presenting cells (APC). Comparison of MHC expression on various types of APC by cytofluorimetry and quantitative immunoprecipitation showed very high expression of class I and class II MHC molecules on DC. Strikingly, examination of class I and class II molecules by isoelectric focusing revealed qualitative differences as well. We show that the surface MHC class I molecules of DC are present in greater quantity and carry on average fewer sialic acids than the same molecules isolated from other APC types such as spleen cells, lipopolysaccharide blasts or concanavalin A blasts. That sialic acids on cell surface molecules, including MHC, may play a role in antigen presentation is suggested by our finding that removal of sialic acids, by neuraminidase, can restore specific responses to nonresponder APC as well.

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Failure and Success in Abolition of Virus‐Specific CTL‐Response Defects by Dendritic Cells

Cited by 27 publications

References 7 publications

A rapid isolation procedure for dendritic cells from mouse spleen by centrifugal elutriation

A rapid isolation procedure for dendritic cells from mouse spleen by centrifugal elutriation

Infection of mature dendritic cells with herpes simplex virus type 1 dramatically reduces lymphoid chemokine-mediated migration

Specific immune responses restored by alteration in carbohydrate chains of surface molecules on antigen‐presenting cells

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