Alloreactivity: An Old Puzzle Revisited

Nagy, Zoltán Á.

doi:10.1111/j.1365-3083.2012.02680.x

Cited by 11 publications

(7 citation statements)

References 69 publications

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“…For the generation of an effective antibody response to a kidney allograft, T‐lymphocyte help to B cells, enhanced by the CD40‐CD40 ligand pathway, is required . However, before this happens, T lymphocytes (CD4+ and CD8+ cells) are primed either by recognition of mismatched HLA antigen epitopes on donor antigen‐presenting cells (APC) (direct allorecognition) or by peptides derived from processed foreign HLA molecules expressed on antigen‐presenting dendritic cells of the recipient (indirect allorecognition) . It is generally acknowledged that, if suppression of the T cell‐dependent immune response by immunosuppressive agents is not sufficient, both (direct and indirect) pathways are active during the whole lifespan of the graft, contributing to chronic organ transplant injury .…”

Section: Recognition Of Foreign Tissue By the Recipient's Immune Systmentioning

confidence: 99%

The possible critical role of T-cell help in DSA-mediated graft loss

et al. 2018

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Summary In this review, we discuss a possible central role of T‐cell help in severe forms of graft damage mediated by donor‐specific HLA antibodies (DSA). Some kidney transplant recipients with pretransplant DSA show a high graft failure rate, whereas in other patients DSA do not harm the transplanted kidney and in most cases, disappear shortly after transplantation. Analyzing 80 desensitized highly immunized kidney transplant recipients and another multicenter cohort of 385 patients with pretransplant HLA antibodies, we reported recently that an ongoing T‐cell help from an activated immune system, as measured by an increased level of soluble CD30 in serum, might be necessary for the DSA to exert a deleterious effect. Patients positive for both pretransplant DSA and sCD30 appear to require special measures, such as the elimination of DSA from the circulation, potent immunosuppression, good HLA‐matching, and intense post‐transplant monitoring, whereas exclusion of DSA‐positive patients from transplantation in the absence of high sCD30 may not be justified in all cases, even if the pretransplant DSA are strong and complement‐activating.

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Section: Recognition Of Foreign Tissue By the Recipient's Immune Systmentioning

confidence: 99%

The possible critical role of T-cell help in DSA-mediated graft loss

et al. 2018

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“…[3][4][5][6][7][8][9] aGvHD is caused by alloreactivity, defined as the donorimmunocompetent cell response against foreign recognized molecules, usually peptides, of the minor and major histocompatibility complex in the host. [10][11][12] The pathophysiology of aGvHD implies multiple tissue and organ damage, mainly affecting the liver, the gastrointestinal tract and/or the skin. 13 The first stage involves the effect of the conditioning regimen and the underlying disease on the host, with the activation of the recipient's APC as well as the release of cytokines and chemokines from the injured tissues.…”

Section: Introductionmentioning

confidence: 99%

Endothelial damage is aggravated in acute GvHD and could predict its development

Mir

Palomo

Rovira

et al. 2017

Bone Marrow Transplant

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The aim of the present study was to explore whether there is enhanced endothelial dysfunction in patients developing acute GvHD (aGvHD) after allogeneic hematopoietic cell transplantation (allo-HCT) and to identify biomarkers with predictive and/or diagnostic value. In in vitro experiments, endothelial cells (ECs) were exposed to serum from patients with (aGvHD, n=31) and without (NoGvHD, n=13) aGvHD, to evaluate changes in surface adhesion receptors, the reactivity of the extracellular matrix by measuring the presence of Von Willebrand factor (VWF) and platelet adhesion, and the activation of intracellular signaling proteins. Plasma levels of VWF, ADAMTS-13, TNF receptor 1 (TNFR1), soluble vascular cell adhesion molecule 1 and soluble intercellular adhesion molecule 1 were also measured. In vitro results showed a more marked proinflammatory and prothrombotic phenotype in ECs in association with aGvHD. Regarding circulating biomarkers, levels of VWF and TNFR1 above an optimal cutoff score, taken independently or combined, at day 7 after allo-HCT, would be able to positively predict that around 90% of patients will develop aGvHD. Our results demonstrate that endothelial damage is aggravated in those allo-HCT recipients developing aGvHD, and that VWF and TNFR1 are promising predictive aGvHD biomarkers. These findings could contribute to improve the understanding of the pathophysiology of aGvHD.

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“…We observed alloreactivity among both CD4 + and CD8 + T-cell subsets, indicating that antigen-display functions of MHCI and MHCII are normal in CD B cells (27). This suggests that CD B cells acquire antigens derived from dying cells and/or through autophagy in an MHCII-dependent pathway (27, 74); conversely, the antigens for MHCI-dependent presentation can be acquired from the intracellular space for canonical presentation and/or from the extracellular space for cross-presentation (27, 75). Unlike allogeneic co-cultures, little or no T-cell proliferation was observed in the autologous T-B co-cultures (Figs.…”

Section: Discussionmentioning

confidence: 99%

Efficient Culture of Human Naive and Memory B Cells for Use as APCs

Watanabe

Yeh

et al. 2016

The Journal of Immunology

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The ability to culture and expand B cells in vitro has become a useful tool for studying human immunity. A limitation of current methods for human B-cell culture is the capacity to support mature B-cell proliferation. We have developed a culture method to support the efficient activation and proliferation of both naïve and memory human B cells. This culture supports extensive B-cell proliferation, with approximately 103-fold increases following 8 days in culture, and 106-fold increases when cultures are split and cultured for 8 more days. In culture, a significant fraction of naïve B cells undergo isotype switching and differentiate into plasmacytes. Culture-derived (CD) B cells are readily cryopreserved, and when recovered, retain their ability to proliferate and differentiate. Significantly, proliferating CD B cells express high levels of MHCII, CD80, and CD86. CD B cells act as APCs and present both alloantigens and microbial antigens to T cells. We are able to activate and expand antigen-specific memory B cells; these cultured cells are highly effective in presenting antigen to T cells. We have characterized the TCR repertoire of rare antigen-specific CD4+ T cells that proliferated in response to tetanus toxoid (TT) presented by autologous CD B cells. TCR Vβ usage by TT-activated CD4+ T cells differs from both resting and unspecifically activated CD4+ T cells. Moreover, we found that TT-specific TCR Vβ usage by CD4+ T cells was substantially different between donors. This culture method provides a platform for studying the BCR and TCR repertoires within a single individual.

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Alloreactivity: An Old Puzzle Revisited

Cited by 11 publications

References 69 publications

The possible critical role of T-cell help in DSA-mediated graft loss

The possible critical role of T-cell help in DSA-mediated graft loss

Endothelial damage is aggravated in acute GvHD and could predict its development

Efficient Culture of Human Naive and Memory B Cells for Use as APCs

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