Immature rat myeloid dendritic cells generated in low-dose granulocyte macrophage-colony stimulating factor prolong donor-specific rat cardiac allograft survival

DePaz, H.A; Oluwole, Olakunle O.; Adeyeri, Ayotunde O.; Witkowski, Piotr; Jin, Mei; Hardy, Mark A.; Oluwole, Soji F.

doi:10.1097/01.tp.0000048380.84355.4a

Cited by 70 publications

(53 citation statements)

References 31 publications

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“…Both observations suggest that DC maturation per se is not necessarily the distinguishing feature of immunogenic as opposed to tolerogenic DCs (46). Despite these reservations, data suggest that immature myeloid precursors of DC suppress T cell activation while immature DCs support Treg development, and mature DCs can override Treg-mediated suppression in vitro and in vivo (47)(48)(49). We had reported that preferential induction of Treg by DCs activated by alternate CD200Rs was an important feature of the effect of CD200 interaction with alternate CD200R isoforms (29).…”

Section: Discussionmentioning

confidence: 77%

An Interaction between CD200 and Monoclonal Antibody Agonists to CD200R2 in Development of Dendritic Cells That Preferentially Induce Populations of CD4+CD25+ T Regulatory Cells

Gorczynski

Khatri

Lee

et al. 2008

The Journal of Immunology

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In previous studies we reported that while interaction between the relatively ubiquitously expressed molecule CD200 and one of its receptors, CD200R1, resulted in direct suppression of alloreactivity, engagement of alternate receptors led instead to altered differentiation of dendritic cells (DCs) from marrow precursors, which could in turn foster development of Foxp3+ regulatory T cells. We have explored this effect of engagement of alternate receptors by using a monoclonal agonist Ab to CD200R2 and investigating expression of TLRs on DCs induced in vivo and in vitro after CD200 stimulation in mice in which the gene encoding CD200R1 was deleted. CD200 stimulation was achieved by using either a soluble form of CD200 (CD200Fc) or overexpression of CD200 as a doxycycline-inducible transgene. Although broadly similar effects were seen, consistent with the hypothesis that triggering of CD200R2 does produce DCs with a characteristic TLR repertoire, there are subtle differences in suppression of alloreactivity achieved by CD200 delivered in these two manners, which is consistent with a complexity of CD200:CD200R engagement not previously appreciated.

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Section: Discussionmentioning

confidence: 77%

An Interaction between CD200 and Monoclonal Antibody Agonists to CD200R2 in Development of Dendritic Cells That Preferentially Induce Populations of CD4+CD25+ T Regulatory Cells

Gorczynski

Khatri

Lee

et al. 2008

The Journal of Immunology

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“…Drugs that prevent full activation of APC during primary sensitization may be better candidates than conventional immunosuppressive agents that broadly inhibit T lymphocytes activation. Indeed, many reports suggest that maintaining DC in an immature or semi-mature stage can be effective in preventing allograft rejection and favor graft tolerance [22,23]. Various compounds such as MMF, vitamin D or glucocorticoids have been shown to inhibit DC maturation, but all these drugs also strongly inhibit T cell activation [24][25][26].…”

Section: Discussionmentioning

confidence: 99%

A new carboxamide compound exerts immuno‐suppressive activity by inhibiting dendritic cell maturation

et al. 2005

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The immunosuppressive properties of a benzamide derivative, JM34, previously characterized as an anti-inflammatory compound are described. The immunosuppressive potential of JM34 was evidenced by inhibition of PBMC proliferation in vitro with an IC 50 of 20 lM. In contrast with classical immunosuppressive drugs, JM34 affected neither cytokine production nor IL-2R expression from activated T cell clones, and displayed only moderate inhibition of IL-2-induced or anti-CD3/anti-CD28-induced proliferation. We investigated its effects on dendritic cells (DC) in vitro. Addition of JM34 during DC maturation inhibited the expression of some maturation markers: specifically, MHC molecule up-regulation was totally inhibited and CD83 expression was significantly reduced, while up-regulation of CD86, CD80 or CD40 was less affected. Moreover, JM34-treated DC showed impaired IL-12 but not IL-10 secretion, and a markedly reduced ability to present antigens to naive T lymphocytes in vitro. We provide evidence that these JM34-induced alterations of DC were associated with a marked inhibition of NF-jB nuclear translocation. Finally, JM34 inhibited delayed type hypersensitivity dose dependently in mice. In conclusion, our data suggest that JM34 inhibited T lymphocyte activation mainly by targeting DC, and thus may represent a new class of therapeutic agents in the fields of transplantation and autoimmune diseases.

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“…Several protocols have been proposed to generate in vitro tolerogenic DCs using specific culture conditions, pharmacologic treatment (exposure to immunosuppressive drugs or cytokines), or genetic manipulation (3)(4)(5)(6)(7)(8)(9). These DCs can be of donor or recipient origin, and their capacity to modulate alloimmune responses and induce tolerance was demonstrated in various experimental transplant models (5,(9)(10)(11)(12)(13)(14). The mode of action of these tolerogenic DCs resides in their ability to induce T cell hyporesponsiveness to the alloantigens and/or to favor the expansion/generation of CD4 +…”

mentioning

confidence: 99%

Combining Autologous Dendritic Cell Therapy with CD3 Antibodies Promotes Regulatory T Cells and Permanent Islet Allograft Acceptance

Baas

Kuhn

Valette

et al. 2014

The Journal of Immunology

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Cell therapy and the use of mAbs that interfere with T cell effector functions constitute promising approaches for the control of allograft rejection. In the current study, we investigated a novel approach combining administration of autologous tolerogenic dendritic cells with short-term treatment with CD3-specific Abs. Permanent acceptance of pancreatic islet allografts was achieved in mice treated with the combination therapy the day before transplantation but not in recipients treated with either therapy alone. The combination treatment induced a marked decrease in T cells infiltrating the allografts and a sustained reduction of antidonor responses. Importantly, CD4+Foxp3+ regulatory T cells appeared to play a crucial role in the long-term graft acceptance. Their frequency increased significantly in the spleen, draining lymph nodes, and transplanted islets and remained elevated over the long term; they exhibited increased donor-specific suppressive functions; and their removal at the time of transplantation abrogated the therapeutic effect of the combined therapy. These results support the therapeutic potential of protocols combining autologous dendritic cells and low-dose CD3 Abs, both currently in clinical development, and that act in synergy to control allogeneic immune responses and favor graft survival in a full-mismatch situation.

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Immature rat myeloid dendritic cells generated in low-dose granulocyte macrophage-colony stimulating factor prolong donor-specific rat cardiac allograft survival

Cited by 70 publications

References 31 publications

An Interaction between CD200 and Monoclonal Antibody Agonists to CD200R2 in Development of Dendritic Cells That Preferentially Induce Populations of CD4+CD25+ T Regulatory Cells

An Interaction between CD200 and Monoclonal Antibody Agonists to CD200R2 in Development of Dendritic Cells That Preferentially Induce Populations of CD4+CD25+ T Regulatory Cells

A new carboxamide compound exerts immuno‐suppressive activity by inhibiting dendritic cell maturation

Combining Autologous Dendritic Cell Therapy with CD3 Antibodies Promotes Regulatory T Cells and Permanent Islet Allograft Acceptance

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