Aplastic Anemia, Histiocytosis and Erythrodermia in Immunologically Deficient Children

We, Hathaway; Jh, Githens; Wr, Blackburn; Fulginiti,; Ch, Kempe

doi:10.1056/nejm196510282731803

Cited by 209 publications

(58 citation statements)

References 13 publications

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“…Host pDCs may not be responsible for the induction of transfusion-associated GVHD in humans. 43,44 It has been shown that TBI plays an important role in the pathogenesis of GVHD; GVHD is less severe in recipients that have had gentle rather than intensive preconditioning treatments. 45,46 TBI activates and damages host tissue to secrete endogenous factors, such as heat-shock proteins and proinflammatory cytokines like tumor necrosis factor-␣ and IL-1.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…1,2 Initially described as erythroderma accompanied by rapidly fatal pancytopenia in immunodeficient patients, the syndrome was subsequently characterized as a form of GVHD following blood transfusion. 3,4 Over the past three decades, the pathophysiology of TA-GVHD has been studied extensively, and the primary mechanism of action attributed to the proliferation of donor T cells in susceptible recipients following transfusion. 5 By empirical experience, irradiation of blood components with either gamma or Xray sources has been established as an effective means to prevent TA-GVHD.…”

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confidence: 99%

Novel processes for inactivation of leukocytes to prevent transfusion-associated graft-versus-host disease

Corash

Lin

2003

Bone Marrow Transplant

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Summary:Transfusion-associated graft-versus-host disease (TA-GVHD) is a serious complication of blood component transfusion therapy. Currently, cellular blood components for patients recognized at risk for TA-GVHD are irradiated prior to transfusion in order to prevent this complication. Considerable progress has been made in elucidating the pathophysiology of this highly morbid complication, but questions as to which patients are at risk and what is the most robust technology to prevent TA-GVHD remain. As new technologies for inactivating or modulating leukocyte function are introduced, the question of how to evaluate these technologies becomes relevant. Over the past two decades, a number of research groups have explored technology to inactivate infectious pathogens and leukocytes contaminating cellular blood components. Few clinicians have an in-depth understanding of the methods or the criteria for selection of how to approach new technologies for leukocyte inactivation with potential to replace current methods. This mini review focuses on the salient aspects of current and evolving technology for prevention of TA-GVHD.

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“…Therapeutic measures, including exchange transfusion of the immunologically immature fetus in utero 8 , routine transfusion of infants suffering from congenital immunological deficiency syndrome 9 , and even of lymphocytes from the maternal to the infant circulatory system 10 can all place infants at risk due to the induction of a GVHD syndrome. In addition, bone marrow transplantation in children with haematological disorders can result in GVHD, and affected infants often survive mild or moderate episodes of the disease 11 .…”

Section: Author Manuscriptmentioning

confidence: 99%

Graft-versus-host disease impairs cerebellar growth

Griffin

Head

Woodward

et al. 1978

Nature

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Aplastic Anemia, Histiocytosis and Erythrodermia in Immunologically Deficient Children

Cited by 209 publications

References 13 publications

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

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

Novel processes for inactivation of leukocytes to prevent transfusion-associated graft-versus-host disease

Graft-versus-host disease impairs cerebellar growth

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