scholarly journals In Vitro Priming of Human T Cells by Dendritic Cells Provides a Screening Tool for Candidate Vaccines for Burkholderia pseudomallei

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 929
Author(s):  
Durga Reddi ◽  
Lydia Durant ◽  
David Bernardo ◽  
Alistair Noble ◽  
Nicholas R. English ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Burkholderia Pseudomallei ◽  
Cellular Response ◽  
Ex Vivo ◽  
Cell Mediated Immunity ◽  
Human T Cell ◽  
Human T Cells

Murine dendritic cells, when pulsed with heat-killed Burkholderia pseudomallei and used to immunise naïve mice, have previously been shown to induce protective immunity in vivo. We have now demonstrated the in vitro priming of naïve human T cells against heat-killed B. pseudomallei, by co-culture with syngeneic B. pseudomallei-pulsed dendritic cells. Additionally, we have enriched the DC fraction such that a study of the differential response induced by pulsed DCs of either myeloid or plasmacytoid lineage in syngeneic human T cells was achievable. Whilst both mDCs and pDCs were activated by pulsing, the mDCs contributed the major response to B. pseudomallei with the expression of the migration marker CCR7 and a significantly greater secretion of the proinflammatory TNFα and IL1β. When these DC factions were combined and used to prime syngeneic T cells, a significant proliferation was observed in the CD4+ fraction. Here, we have achieved human T cell priming in vitro with unadjuvanted B. pseudomallei, the causative organism of melioidosis, for which there is currently no approved vaccine. We propose that the approach we have taken could be used to screen for the human cellular response to candidate vaccines and formulations, in order to enhance the cell-mediated immunity required to protect against this intracellular pathogen and potentially more broadly against other, difficult-to-treat intracellular pathogens. To date, the polysaccharide capsule of B. pseudomallei, fused to a standard carrier protein, e.g., Crm, looks a likely vaccine candidate. Dendritic cells (DCs), providing, as they do, the first line of defence to infection, process and present microbial products to the immune system to direct downstream immune responses. Here, we have sought to use DCs ex vivo to identify immunogenic products from heat-killed B. pseudomallei. Using practical volumes of fresh human donor blood, we show that heat-killed B. pseudomallei activated and stimulated the expression of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 from both myeloid and plasmacytoid DCs. Furthermore, B. pseudomallei-pulsed DCs cultured with naïve syngeneic T cells ex vivo, induced the activation and proliferation of the CD4+ T-cell population, which was identified by cell surface marker staining using flow cytometry. Thus, both DC subsets are important for driving primary T helper cell responses to B. pseudomallei in healthy individuals and have the potential to be used to identify immunogenic components of B. pseudomallei for future therapies and vaccines.

Modified myeloid dendritic cells act as regulatory dendritic cells to induce anergic and regulatory T cells

Blood ◽  
2003 ◽  
Vol 101 (9) ◽  
pp. 3581-3589 ◽  
Author(s):  
Katsuaki Sato ◽  
Naohide Yamashita ◽  
Masanori Baba ◽  
Takami Matsuyama
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Allogeneic Transplantation ◽  
Cell Mediated Immunity ◽  
Myeloid Dendritic Cells ◽  
Mhc Molecules ◽  
Human T Cells ◽  
Novel Strategy

To exploit a novel strategy to regulate T cell–mediated immunity, we established human and murine modified dendritic cells (DCs) with potent immunoregulatory properties (designed as regulatory DCs), which displayed moderately high expression levels of major histocompatibility complex (MHC) molecules and extremely low levels of costimulatory molecules compared with their normal counterparts. Unlike human normal DCs, which caused the activation of allogeneic CD4+ and CD8+ T cells, human regulatory DCs not only induced their anergic state but also generated CD4+ or CD8+regulatory T (Tr) cells from their respective naive subsets in vitro. Although murine normal DCs activated human xenoreactive T cells in vitro, murine regulatory DCs induced their hyporesponsiveness. Furthermore, transplantation of the primed human T cells with murine normal DCs into severe combined immunodeficient (SCID) mice enhanced the lethality caused by xenogeneic graft-versus-host disease (XGVHD), whereas transplantation of the primed human T cells with murine regulatory DCs impaired their ability to cause XGVHD. In addition, a single injection of murine regulatory DCs following xenogeneic or allogeneic transplantation protected the recipients from the lethality caused by XGVHD as well as allogeneic acute GVHD. Thus, the modulation of T cell–mediated immunity by regulatory DCs provides a novel therapeutic approach for immunopathogenic diseases.

scholarly journals Dendritic cells transduced by multiply deleted HIV-1 vectors exhibit normal phenotypes and functions and elicit an HIV-specific cytotoxic T-lymphocyte response in vitro

Blood ◽  
2000 ◽  
Vol 96 (4) ◽  
pp. 1327-1333 ◽  
Author(s):  
Andreas Gruber ◽  
June Kan-Mitchell ◽  
Kelli L. Kuhen ◽  
Tetsu Mukai ◽  
Flossie Wong-Staal
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Ex Vivo ◽  
T Cell Response ◽  
Adoptive T Cell Therapy ◽  
Cytotoxic T Cell ◽  
T Cell Therapy ◽  
Hiv 1

Abstract Dendritic cells (DCs) genetically modified to continually express and present antigens may be potent physiologic adjuvants for induction of prophylactic or therapeutic immunity. We have previously shown that an env and nef deleted HIV-1 vector (HIV-1ΔEN) pseudotyped with VSV-G transduced monocyte-derived macrophages as well as CD34+ precursors of DCs. Here we extended these findings with HIV-1ΔEN to highly differentiated human DCs derived in culture from circulating monocytes (DCs). In addition, a new vector derived from HIV-1ΔEN but further deleted in its remaining accessory genes vif, vpr, and vpu(HIV-1ΔEN V3) was also tested. Both vectors efficiently transduced DCs. Transduction of DCs did not significantly alter their viability or their immunophenotype when compared with untransduced DCs. Furthermore, the phagocytic potential of immature DCs, as well as their ability to differentiate into mature DCs capable of stimulating T-cell proliferation, was not affected. Finally, DCs transduced by the HIV-1ΔEN vector were able to elicit a primary antiviral cytotoxic T-cell response in autologous CD8 T cells. These results suggest that HIV-1–based vectors expressing viral antigens may be useful for in vivo active immunization as well as ex vivo priming of cytotoxic T cells for adoptive T-cell therapy.

scholarly journals Dendritic cells transduced by multiply deleted HIV-1 vectors exhibit normal phenotypes and functions and elicit an HIV-specific cytotoxic T-lymphocyte response in vitro

Blood ◽  
2000 ◽  
Vol 96 (4) ◽  
pp. 1327-1333 ◽  
Author(s):  
Andreas Gruber ◽  
June Kan-Mitchell ◽  
Kelli L. Kuhen ◽  
Tetsu Mukai ◽  
Flossie Wong-Staal
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Ex Vivo ◽  
T Cell Response ◽  
Adoptive T Cell Therapy ◽  
Cytotoxic T Cell ◽  
T Cell Therapy ◽  
Hiv 1

Dendritic cells (DCs) genetically modified to continually express and present antigens may be potent physiologic adjuvants for induction of prophylactic or therapeutic immunity. We have previously shown that an env and nef deleted HIV-1 vector (HIV-1ΔEN) pseudotyped with VSV-G transduced monocyte-derived macrophages as well as CD34+ precursors of DCs. Here we extended these findings with HIV-1ΔEN to highly differentiated human DCs derived in culture from circulating monocytes (DCs). In addition, a new vector derived from HIV-1ΔEN but further deleted in its remaining accessory genes vif, vpr, and vpu(HIV-1ΔEN V3) was also tested. Both vectors efficiently transduced DCs. Transduction of DCs did not significantly alter their viability or their immunophenotype when compared with untransduced DCs. Furthermore, the phagocytic potential of immature DCs, as well as their ability to differentiate into mature DCs capable of stimulating T-cell proliferation, was not affected. Finally, DCs transduced by the HIV-1ΔEN vector were able to elicit a primary antiviral cytotoxic T-cell response in autologous CD8 T cells. These results suggest that HIV-1–based vectors expressing viral antigens may be useful for in vivo active immunization as well as ex vivo priming of cytotoxic T cells for adoptive T-cell therapy.

Quantitative Assessment of the Impact of Ex Vivo Manipulation on the In Vivo Functionality of Human T Cells in RAG2−/− γc−/− mice.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 450-450
Author(s):  
Rozemarijn S. van Rijn ◽  
Elles R. Simonetti ◽  
Gert Storm ◽  
Mark Bonyhadi ◽  
Anton Hagenbeek ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Ex Vivo ◽  
T Cell Subsets ◽  
Critical Parameters ◽  
In Vivo Evaluation ◽  
Human T Cells ◽  
The Impact

Abstract T cells retrovirally modified to express therapeutic genes encoding cytokines, exogenous TCRs or suicide molecules represent a novel class of immune therapeutics of great potency. However, recent clinical trials using retrovirally-modified T cells have indicated that T cells exhibit a diminished reactivity upon ex vivo manipulation. In addition, virus-specific memory T cells seem to be lost during gene transfer. In a BNML rat model we have shown that the culture procedure is one of the critical parameters. To preserve T cell reactivity, reliable models are required which permit readout of human T cell activity. We recently developed a huPBMC-RAG2−/−γc−/− mouse model for xenogeneic graft-versus-host disease (xGVHD), in which iv injection of 15 x 106 human T cells into RAG2−/−γc−/− mice consistently leads to high level engraftment and lethal xGVHD within 3 weeks in 80% of mice (van Rijn et al, Blood 2003). We have now used this model to analyze in vivo functionality of human T cells following different ex vivo culture procedures. For this, we cultured human T cells for 7 days with either of the two currently available clinically applicable stimulation conditions: 1) via CD3 and 2) via CD3/CD28. In addition, we included CD3/CD28/4-1BB stimulation to explore the effect of extensive costimulation. Mice were injected with escalating doses T cells. HuCD45+ cells in peripheral blood were measured by FACS. Lethal xGVHD occurred at only 6 times (90.106) the dose of fresh cells for CD3-stimulated T cells and 3 times for CD3/28- or CD3/28/4-1BB-stimulated cells. About 20% of surviving mice developed chronic xGVHD, independent of culture method. While lethal xGVHD was always associated with very high levels of engraftment (up to 95%) engraftment levels in chronic mice ranged from 1–75%. To compare the impact of the different culture conditions on in vivo T cell function, we analyzed engraftment potential. The fraction of huCD45+ cells was plotted against the time and the areas under the curves were compared. Based on a total of 68 mice, statistical analysis showed a 2-fold improvement of engraftment potential for C28-costimulated human T cells compared to CD3-stimulated cells (P<0.0001). Additional ligation of 4-1BB did not increase engraftment potential. In addition, different T cell subsets (naïve, memory, effector) were monitored based on the combined expression of CD45RA, CD27 and CCR7. For all primary T cells and variably cultured T cells, a strikingly similar pattern was observed in vivo. After 3 weeks mainly effector and memory effector T cells (both CD4+ and CD8+) could be detected, suggesting a (xeno-)antigen-driven survival and expansion. This was a very consistent observation independent of donor, culture condition, engraftment level or severity of disease. In conclusion, in vitro costimulation preserves in vivo functionality of human T cells and should therefore be included in future clinical protocols for ex vivo manipulation of T cells. These data show the feasibility to use the huPBMC-RAG2−/−γc−/− model for in vivo evaluation of in vitro effects on human T cells. This model is the most sensitive to date for in vivo evaluation of human T cells and will be a promising new tool for the study of human T cells in, for instance, autoimmune disease, cancer and infectious diseases like AIDS.

scholarly journals Analysis of Apoptosis of Memory T Cells and Dendritic Cells during the Early Stages of Viral Infection or Exposure to Toll-Like Receptor Agonists

2010 ◽  
Vol 84 (10) ◽  
pp. 4866-4877 ◽  
Author(s):  
Kapil Bahl ◽  
Anette Hüebner ◽  
Roger J. Davis ◽  
Raymond M. Welsh
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Ex Vivo ◽  
Annexin V ◽  
Poly I:C ◽  
Type I ◽  
Memory T Cell ◽  
Lcmv Infection

ABSTRACT Profound type I interferon (IFN-I)-dependent attrition of memory CD8 and CD4 T cells occurs early during many infections. It is dramatic at 2 to 4 days following lymphocytic choriomeningitis virus (LCMV) infection of mice and can be elicited by the IFN-inducing Toll receptor agonist poly(I:C). We show that this attrition occurs in many organs, indicating that it is due to T cell loss rather than redistribution. This loss correlated with elevated intracellular staining of T cells ex vivo for activated caspases but with only low levels of ex vivo staining with annexin V, probably due to the rapid clearance of apoptotic cells in vivo. Instead, a high frequency of annexin V-reactive CD8α+ dendritic cells (DCs), which are known to be highly phagocytic, accumulated in the spleen as the memory T cell populations disappeared. After short in vitro incubation, memory phenotype T cells isolated from LCMV-infected mice (day 3) or mice treated with poly(I:C) (12 h) displayed substantial DNA fragmentation, as detected by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, compared to T cells isolated from uninfected mice, indicating a role for apoptosis in the memory T cell attrition. This apoptosis of memory CD8 T cells early during LCMV infection was reduced in mice lacking the proapoptotic molecule Bim. Evidence is presented showing that high levels of T cell attrition, as found in young mice, correlate with reduced immunodomination by cross-reactive memory cells.

CD27 costimulation augments the survival and antitumor activity of redirected human T cells in vivo

Blood ◽  
2012 ◽  
Vol 119 (3) ◽  
pp. 696-706 ◽  
Author(s):  
De-Gang Song ◽  
Qunrui Ye ◽  
Mathilde Poussin ◽  
Gretchen M. Harms ◽  
Mariangela Figini ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antitumor Activity ◽  
Car T Cells ◽  
Human T Cell ◽  
Human T Cells ◽  
Car T ◽  
Cd27 Costimulation

AbstractThe costimulatory effects of CD27 on T lymphocyte effector function and memory formation has been confined to evaluations in mouse models, in vitro human cell culture systems, and clinical observations. Here, we tested whether CD27 costimulation actively enhances human T-cell function, expansion, and survival in vitro and in vivo. Human T cells transduced to express an antigen-specific chimeric antigen receptor (CAR-T) containing an intracellular CD3 zeta (CD3ζ) chain signaling module with the CD27 costimulatory motif in tandem exerted increased antigen-stimulated effector functions in vitro, including cytokine secretion and cytotoxicity, compared with CAR-T with CD3ζ alone. After antigen stimulation in vitro, CD27-bearing CAR-T cells also proliferated, up-regulated Bcl-XL protein expression, resisted apoptosis, and underwent increased numerical expansion. The greatest impact of CD27 was noted in vivo, where transferred CAR-T cells with CD27 demonstrated heightened persistence after infusion, facilitating improved regression of human cancer in a xenogeneic allograft model. This tumor regression was similar to that achieved with CD28- or 4-1BB–costimulated CARs, and heightened persistence was similar to 4-1BB but greater than CD28. Thus, CD27 costimulation enhances expansion, effector function, and survival of human CAR-T cells in vitro and augments human T-cell persistence and antitumor activity in vivo.

scholarly journals Cure of disseminated xenografted human Hodgkin's tumors by bispecific monoclonal antibodies and human T cells: the role of human T-cell subsets in a preclinical model

Blood ◽  
1996 ◽  
Vol 87 (7) ◽  
pp. 2930-2937 ◽  
Author(s):  
C Renner ◽  
S Bauer ◽  
U Sahin ◽  
W Jung ◽  
R van Lier ◽  
...  
Keyword(s):  
T Cells ◽  
Monoclonal Antibodies ◽  
T Cell ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Scid Mice ◽  
T Cell Subsets ◽  
Human T Cell ◽  
Human T Cells

Cure of a single established human Hodgkin's tumor growing subcutaneously in severe combined immunodeficient (SCID) mice can be achieved with a complex protocol using two bispecific monoclonal antibodies (Bi-MoAb) directed against the Hodgkin's associated CD30 antigen and the T-cell triggering molecules CD3 and CD28, respectively, together with human T cells prestimulated in vitro with Bi-MoAbs in the presence of CD30+ cells. To adapt this model to the clinical situation, disseminated tumors were established in SCID mice by intravenous injection of 2 x 10(7) cells of the Hodgkin's derived cell line L540CY. Treatment of SCID mice bearing disseminated CD30+ Hodgkin's tumors with the combination of CD3/CD30 and CD28/CD30 Bi-MoAbs and naive (ie, not in vitro prestimulated) human T cells resulted in the cure of all appropriately treated animals. T lymphocytes obtained from patients with advanced stage untreated Hodgkin's disease were as effective as lymphocytes from healthy controls. Treatment was effective even when delayed until 2 weeks after tumor inoculation, and application of Bi- MoAbs into SCID mice with circulating human T cells was as effective as injecting the Bi-MoAbs before the lymphocytes. Treatment results with isolated CD4+ and CD8+ human T cells suggest that both subsets are necessary for the Bi-MoAb mediated cure of xenografted human tumors in vivo. The efficacy and practicability of this preclinical immunotherapy protocol support and form the basis for the clinical evaluation of this approach in patients with Hodgkin's disease resistant to standard therapy.

scholarly journals Transcription factor GATA-1 potently represses the expression of the HIV-1 coreceptor CCR5 in human T cells and dendritic cells

Blood ◽  
2005 ◽  
Vol 106 (10) ◽  
pp. 3440-3448 ◽  
Author(s):  
Mark S. Sundrud ◽  
Scott E. VanCompernolle ◽  
Karla A. Eger ◽  
Tullia C. Bruno ◽  
Arun Subramaniam ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Chemokine Receptor ◽  
Molecular Mechanisms ◽  
T Cell Subsets ◽  
Critical Determinant ◽  
Human T Cell ◽  
Human T Cells ◽  
Hiv 1

AbstractCC chemokine receptor 5 (CCR5) is the major HIV-1 coreceptor and its expression levels are a critical determinant of HIV-1 infection. However, the molecular mechanisms of CCR5 regulation in primary targets of HIV-1 remain unknown. Despite binding to conserved DNA elements, we show that the transcription factors GATA binding protein 1 (GATA-1) and GATA-3 differentially suppress the expression of CCR5 in stem-cell–derived dendritic cells and primary human T-cell subsets. In addition, GATA-1 expression was also more potent than GATA-3 in suppressing T helper 1 (Th1)–associated genes, interferon-γ (IFNγ), and CXC chemokine receptor-3 (CXCR3). GATA-1, but not GATA-3, potently suppressed CCR5 transcription, thereby rendering human T cells resistant to CCR5-tropic HIV-1 infection. However, GATA-1 could also serve as a surrogate for GATA-3 in its canonic role of programming Th2 gene expression. These findings provide insight into GATA-3–mediated gene regulation during T-cell differentiation. Importantly, decoding the mechanisms of GATA-1–mediated repression of CCR5 may offer an opportunity to develop novel approaches to inhibit CCR5 expression in T cells.

Ex Vivo Generation Of Functional Plasmacytoid and Myeloid Dendritic Cells Is Strongly Promoted By The Aryl Hydrocarbon Receptor Antagonist Stemregenin 1

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2025-2025
Author(s):  
Soley Thordardottir ◽  
Hangalapura Basav N. ◽  
Tim Hutten ◽  
Marta Cossu ◽  
Jan Spanholtz ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Ex Vivo ◽  
T Cell Responses ◽  
Cell Responses ◽  
Aryl Hydrocarbon ◽  
Hla Dr ◽  
Cd34 Cells

Abstract The prominent role of dendritic cells (DCs) in T cell activation is the rational for DC-based immunotherapy of cancer and infectious diseases. In cancer, DC therapy aims to induce tumor-specific effector T cell responses that can reduce or eliminate the tumor, and to develop immunological memory to control tumor relapse. So far, the vast majority of DC vaccination studies have been performed with DCs differentiated from monocytes (Mo-DCs) that are loaded with tumor-associated antigens (TAAs) or minor histocompatibility antigens (MiHA). This strategy has been reported to induce the expansion of antigen-specific CD4+ and/or CD8+ T cells in the majority of patients, however only a fraction of the patients develop clinical responses. Strategies to improve the potency of DC-based vaccines are to increase the stimulatory and migratory capacity of Mo-DCs, or to use alternative DC subtypes, such as naturally circulating plasmacytoid DCs (pDCs), BDCA1+ myeloid DCs (mDCs) or BDCA3+ mDCs. These DC subsets are potent inducers of antigen-specific T cell responses, and are therefore attractive cells to exploit for DC-based therapy. However, since their frequency in blood is very low, it is a challenge to obtain high enough numbers for immunotherapy. It would be advantageous if DCs, which are phenotypically and functionally similar to blood pDCs and mDCs, could be generated from CD34+ hematopoietic progenitor cells (HPCs). Interestingly, recent findings have indicated that the aryl hydrocarbon receptor (AhR) not only regulates toxic effects of environmental contaminants, but also plays a role in modulating hematopoiesis and the immune system. For instance, it has been reported that StemRegenin 1 (SR1), a small molecule inhibitor of AhR, promotes the ex vivo expansion of human CD34+ HPCs that are able to effectively engraft immunodeficient mice. Furthermore, differentiation of Langerhans cells and monocytes in vitro from HPCs can be inhibited by the addition of the AhR agonist VAF347. In light of these data, we investigated if we could generate DC subsets from CD34+ HPCs by supplementing SR1. Therefore, we cultured CD34+ HPCs in medium containing SCF, Flt3L, IL-6, TPO supplemented with 1 μM SR1 or DMSO as control. Interestingly, addition of SR1 explicitly promoted the emergence of pDCs (CD11c-HLA-DR+CD123hiBDCA2+BDCA4+ cells), BDCA1+ mDCs (Lin1-HLA-DR+BDCA1+BDCA3- cells) and BDCA3+ mDCs (Lin1-HLA-DR+BDCA1-BDCA3+ cells). After three weeks of culture, the frequency of these DC subsets was significantly higher in cultures with SR1 compared to control conditions; 2.9% vs. 0.04% for pDCs, 4.6% vs. 0.5% for BDCA1+ mDCs and 1.1% vs. 0.1% for BDCA3+ mDCs (n=3-5 donors). The average yield after three weeks of culture with SR1 starting from 105 CD34+ UCB cells was 3.8x106 pDCs, 5.3x106 BDCA1+ mDCs and 1.2x106 BDCA3+ mDCs (n=3-5 donors). Furthermore, SR1 also promoted the differentiation of DC subsets from CD34+ cells obtained from peripheral blood of G-CSF-mobilized donors. The average frequency of DCs in these SR1-cultures was 4.7%, 3.8% and 0.9% for pDCs, BDCA1+ and BDCA3+ mDCs, respectively (n=3 donors), which is comparable to the frequency obtained from UCB CD34+ cells. But the expansion potential of G-CSF-mobilized blood CD34+ HPCs was lower than that of UCB CD34+ cells, resulting in average DC yields of 0.6x106, 0.5x106 and 0.1x106 from 105 CD34+ cells (n=3). Flow cytometry analysis demonstrated that the SR1-induced pDCs and mDCs are phenotypically comparable to their naturally occurring counterpart in blood. Furthermore, the ex vivo-generated pDCs potently responded to stimulation with TLR7 and TLR9 ligands by secreting high amounts of IFN-α and upregulating CD83, CD80, CD86 and CCR7. The HPC-mDC subsets also upregulate CD80 and CD83 upon TLR3, TLR4 or TLR7/8 ligation. Finally, both the ex vivo-generated pDCs and mDCs induced potent allogeneic T cell responses and activated CD8+ effector T cells against hematopoietic-restricted MiHA. These findings demonstrate that our SR1 culture system not only allows detailed study of DC differentiation and molecular regulations in vitro, but it also offers the opportunity to evaluate the in vivo efficacy of cultured DC subsets upon vaccination into patients with cancer and viral infections. Disclosures: Spanholtz: Glycostem Therapeutics: Employment.

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