Promotion of Long-Term Heart Allograft Survival by Combination of Mobilized Donor Plasmacytoid Dendritic Cells and Anti-CD154 Monoclonal Antibody

Björck, Pia; Coates, P. Toby; Wang, Z.; Duncan, F. Jason; Thomson, Angus W.

doi:10.1016/j.healun.2004.10.007

Cited by 39 publications

(31 citation statements)

References 15 publications

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“…Likewise, a single preoperative infusion of donor-mobilized immature pDCs in combination with anti-CD154 monoclonal antibody was able to effectively suppress allograft rejection and prolonged graft survival in mice. 90 These findings are concordant with a recent study in humans that examined total peripheral blood DC numbers in patients with clinical heart transplantation, revealing significantly diminished DC frequency 1 week after heart transplantation, which probably reflects immunologic quiescence through adequate immunosuppression. 91 In summary, adoptive transfer of preprimed (tolerogenic) DCs seems to hold great promise for preventing graft rejection after cardiac transplantation.…”

Section: Dc-targeted Therapeutic Opportunities In Cvd Targeting Dcs Isupporting

confidence: 91%

Dendritic Cells in Cardiovascular Diseases

et al. 2013

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Section: Dc-targeted Therapeutic Opportunities In Cvd Targeting Dcs Isupporting

confidence: 91%

Dendritic Cells in Cardiovascular Diseases

et al. 2013

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“…Moreover, donor-derived preplasmacytoid DC infused 7 days before transplant significantly prolong subsequent heart allograft survival (from 9 to 22 days) in the absence of immunosuppressive therapy (21). As with myeloid DC, this effect is markedly enhanced by anti-CD154 mAb administration (22). Thus it seems that both myeloid and plasmacytoid DC can serve as tolerogenic DC, and that maturation by itself is not the distinguishing feature that separates their immunogenic from their tolerogenic function.…”

Section: Which DC Are Tolerogenic?mentioning

confidence: 99%

Dendritic Cells: Tools and Targets for Transplant Tolerance

Barratt‐Boyes

Thomson

2005

American Journal of Transplantation

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“…17 pDCs mediate tolerance and prolong survival of cardiac allografts. 11,18,19 Several recent clinical observations also suggest that pDCs play important regulatory roles in transplant outcome. An increased ratio of pDCs/cDCs is associated with the successful withdrawal of immunosuppressants after liver transplants.…”

Section: Introductionmentioning

confidence: 99%

“…15 In experimental cardiac transplantation, pDCs mediate tolerance and prolong survival of allografts. 11,18,19 It has been suggested that pDCs functioning as APCs generate suppressive or regulatory T cells that mediate tolerance. 12,13,[16][17][18] In contrast, our study showed that alloantigen-presenting pDCs were incapable of suppressing activation of alloreactive T cells but, instead, induced immunity even in the absence of other APC subsets.…”

mentioning

confidence: 99%

Plasmacytoid dendritic cells prime alloreactive T cells to mediate graft-versus-host disease as antigen-presenting cells

Koyama

Hashimoto

Aoyama

et al. 2009

Blood

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Dendritic cells (DCs) can be classified into 2 distinct subsets: conventional DCs (cDCs) and plasmacytoid DCs (pDCs). cDCs can prime antigen-specific T-cell immunity, whereas in vivo function of pDCs as antigen-presenting cells remains controversial. We evaluated the contribution of pDCs to allogeneic T-cell responses in vivo in mouse models of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation by an add-back study of MHCexpressing pDCs into major histocompatibility complex-deficient mice that were resistant to GVHD. Alloantigen expression on pDCs alone was sufficient to prime alloreactive T cells and cause GVHD. An inflammatory environment created by host irradiation has the decisive role in maturing pDCs for T-cell priming but this process does not require Toll-like receptor signaling. Thus, functional outcomes of pDC-T-cell interactions depend on the immunologic context of encounter. To our knowledge, these results are the first to directly demonstrate an in vivo pathogenic role of pDCs as antigenpresenting cells in an antigen-specific T cell-mediated disease in the absence of other DC subsets and to provide important insight into developing strategies for tolerance induction in transplantation. IntroductionThe interaction of naive T cells and dendritic cells (DCs) is essential for initiating primary immune responses. DCs can be divided into 2 distinct subsets: conventional DCs (cDCs) and plasmacytoid DCs (pDCs) according to their immunophenotype and functional properties. 1-3 pDCs represent a CD11c int B220 ϩ DC subset that differs from the CD11c high B220 Ϫ major histocompatibility complex (MHC) class II high cDCs, commonly viewed as the classic stimulators of naive T cells. One distinctive feature of pDCs is their capacity to rapidly produce high levels of type I interferon (IFN) in response to viral and bacterial stimuli, highlighting the importance of pDCs in innate immune responses. 2-8 pDCs express low levels of surface MHC and classical costimulatory molecules; therefore, they are poor T-cell stimulators. [5][6][7][8][9][10][11] In contrast, pDCs matured with CD40 ligands or Toll-like receptor (TLR) ligands are potent antigen-presenting cells (APCs), capable of stimulating naive T-cell proliferation and differentiation to helper, killer, memory, and regulatory T cells in vitro. 7,12,13 In vivo, injection of pDCs activated by synthetic oligodeoxynucleotides containing unmethylated cytosine-guanine motifs (CpG), but not immature pDCs, is capable of eliciting antigen-specific CD8 ϩ T-cell responses. 10,14 On the other hand, OVA-pulsed pDCs protected mice against OVA-induced asthma development. 15 pDCs in the tumordraining lymph nodes express indole 2, 3-dioxygenase, and suppress antitumor T-cell responses. 16 In patients with ovarian cancer, large numbers of pDCs, which induced interleukin 10 (IL10)-producing regulatory T cells, were found in ascites. 17 pDCs mediate tolerance and prolong survival of cardiac allografts. 11,18,19 Several recent clinical observations...

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Promotion of Long-Term Heart Allograft Survival by Combination of Mobilized Donor Plasmacytoid Dendritic Cells and Anti-CD154 Monoclonal Antibody

Cited by 39 publications

References 15 publications

Dendritic Cells in Cardiovascular Diseases

Dendritic Cells in Cardiovascular Diseases

Dendritic Cells: Tools and Targets for Transplant Tolerance

Plasmacytoid dendritic cells prime alloreactive T cells to mediate graft-versus-host disease as antigen-presenting cells

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