Bridging channel dendritic cells induce immunity to transfused red blood cells

Calabrό, Samuele; Gallman, Antonia; Gowthaman, Uthaman; Liu, Dong; Chen, Pei; Liu, Jingchun; Krishnaswamy, Jayendra Kumar; Nascimento, Manuela Sales Lima; Xu, Lan; Patel, Seema R.; Williams, Adam; Tormey, Christopher A.; Hod, Eldad A.; Spitalnik, Steven L.; Zimring, James C.; Hendrickson, Jeanne E.; Stowell, Sean R.; Eisenbarth, Stephanie C.

doi:10.1084/jem.20151720

Cited by 89 publications

(126 citation statements)

References 39 publications

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“…10 In agreement with these findings, the splenic T cell subsets were shown to be pivotal for antibody production against both autologous and allogeneic platelet membrane antigens.…”

Section: Letters To the Editorsupporting

confidence: 53%

Absence of the spleen and the occurrence of primary red cell alloimmunization in humans

et al. 2017

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“…10 In agreement with these findings, the splenic T cell subsets were shown to be pivotal for antibody production against both autologous and allogeneic platelet membrane antigens.…”

Section: Letters To the Editorsupporting

confidence: 53%

Absence of the spleen and the occurrence of primary red cell alloimmunization in humans

et al. 2017

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“…In addition to expression of co-stimulatory molecules, a balanced release of cytokines and chemokines by DC is also crucial for directing multiple immune pathways [93]. I found minimal modulation of cytokine responses following exposure to PRBC alone, however, both mDC and BDCA3 + DC responses to polyI:C and LPS were suppressed in the presence of PRBC.…”

Section: Prbc Storage Was Associated With Increased Erythrophagocytosismentioning

confidence: 92%

“…Erythrophagocytosis by murine plasmacytoid (p)DC particularly in costimulation with TLR3 agonist, polyinosinic-polycytidylic acid (polyI:C)-driven inflammation has been reported [91]. Murine studies have also demonstrated that splenic DC are important for outcomes in terms of alloimmunisation [92,93].…”

Section: In-vitro and In-vivo Models Of Prbc Transfusion (Related To mentioning

confidence: 99%

“…Modulation of DC maturation and activation following exposure to either clinical PRBC [84,90,92,93] or PC [162] or PC supernatants containing soluble factors [162,168] has been reported. Despite these studies, receptors or mechanisms involved in the interaction between blood components and DC resulting in transfusion-mediated immune modulation of DC function were not explored.…”

Section: Introductionmentioning

confidence: 99%

“…Murine studies have reported that splenic DC are important for outcomes in terms of alloimmunisation [92,93]. Despite these murine studies, our understanding of whether DC play a role in poor patient outcomes following PRBC transfusion remains largely undefined.…”

Section: Introductionmentioning

confidence: 99%

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Characterisation of dendritic cell immune profile in models of transfusion

Ki¹

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Blood transfusion modulates recipients' immune responses sometimes resulting in poor clinical outcomes. Further, transfusion with blood products at date-of-expiry has been associated with exacerbation of this concerning problem. In-vitro studies have demonstrated exposure to packed red blood cell (PRBC) and platelet products modulate the responses of leukocytes, however, there are limited studies on the impact of transfusion on dendritic cells (DC). Despite DC being central to the immune response, their role in transfusion-related immune modulation remains largely undefined. I hypothesised that exposure to blood components changes DC phenotype and function, which could be one mechanism underpinning transfusion-related immune modulation. The potential for blood components (PRBC, buffy-coat-derived platelet concentrates (PC) and cryopreserved platelets (cryo-PLT)) to modulate responses of myeloid dendritic cells ii whether blood components exposing F-actin for Clec9A ligation were present within the blood product. rhClec9A did not bind fresh or stored PRBC, and this outcome was supported by the lack of detection of F-actin. Although, no binding of rhClec9A to PC or cryo-PLT was demonstrated, F-actin was detected on both types of platelet products. As binding of rhClec9A to PRBC, PC or cryo-PLT was not detected, EDTA blood collection tubes were used for the remainder of the study under the premise that lack of expression of this receptor would not impact on outcomes in my transfusion models.I assessed the impact of fresh and/or stored blood products on mDC and BDCA3 + DC surface antigen and inflammatory profile using a human in-vitro whole blood model of transfusion. In parallel, to model the processes associated with viral or bacterial infection, polyinosinic:polycytidylic acid (polyI:C) or lipopolysaccharide (LPS) was added respectively. Exposure to PRBC and PC predominately suppressed surface antigen expression (CD40, CD80, CD83 and CD86) and inflammatory mediator production (interleukin (IL)-6, IL-8, IL-12, tumour necrosis factor-α and interferon-gamma inducible protein-10 or IL-10) on both DC subsets. These changes were often more evident in the presence of polyI:C and LPS, and when DC were exposed to stored PRBC. Similar modulation was evident for BDCA3 + DC when exposed to cryo-PLT alone and cryo-PLT in the presence of polyI:C and LPS. The impact of blood transfusion on the overall inflammatory response by leukocytes was also examined. The immunomodulatory effect of transfusion in-vitro was more pronounced in the presence of polyI:C and LPS. For PRBC, an additional erythrophagocytosis assay was conducted where the uptake of stored PRBC by mDC and BDCA3 + DC was significantly increased in comparison to fresher PRBC.This study provided the first evidence that exposure of PRBC, PC and cryo-PLT modulates mDC and/or BDCA3 + DC maturation and activation. The changes were more pronounced when modelling processes associated with concurrent viral or bacterial infection.Experimental evidence suggested that mod...

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The unexpected contribution of conventional type 1 dendritic cells in driving antibody responses

2021

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Antibodies are hallmarks of most effective vaccines. For successful T-dependent antibody responses, conventional dendritic cells (cDC) have been largely attributed the role of priming T cells. By contrast, follicular dendritic cells and macrophages have been seenas responsible for B cell activation, due to their strategic location within secondary lymphoid tissues and capacity to present native antigen to B cells. This review summarizes the mounting evidence that cDC can also present native antigen to B cells. cDC2 have been the main subset linked to humoral responses, based largely on their favorable location, capacity to prime CD4 + T cells, and ability to present native antigen to B cells. However, studies using strategies to deliver antigen to receptors on cDC1, reveal this subset can also contribute to naïve B cell activation, as well as T cell priming. cDC1 location within lymphoid tissues reveals their juxtaposition to B cell follicles, with ready access to B cells for presentation of native antigen. These findings support the view that both cDC1 and cDC2 are capable of initiating humoral responses provided antigen is captured by relevant surface receptors attuned to this process. Such understanding is fundamental for the development of innovative humoral vaccination approaches.

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Bridging channel dendritic cells induce immunity to transfused red blood cells

Abstract: Calabro et al. show that 33D1+ dendritic cells present in the bridging channel of the spleen are essential for alloantibody response to transfused red blood cells.

Cited by 89 publications

References 39 publications

Absence of the spleen and the occurrence of primary red cell alloimmunization in humans

Absence of the spleen and the occurrence of primary red cell alloimmunization in humans

Characterisation of dendritic cell immune profile in models of transfusion

The unexpected contribution of conventional type 1 dendritic cells in driving antibody responses

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