The Influence of HIA and ABO Antigens on Graft Rejection and Survival

Sanfilippo, Fred

doi:10.1016/s0272-2712(18)30540-7

Cited by 5 publications

(3 citation statements)

References 74 publications

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“…Generally, ABO‐mismatch and disparity in MHC surface antigens are well‐known to influence outcomes of transplanted tissues resulting in their use as predictors for allograft survival . In liver transplantation, however, positive cross‐matches appear more relevant than MHC or even ABO compatibility, highlighting the organ's tolerogenic properties .…”

Section: Discussionmentioning

confidence: 99%

“…Generally, ABO-mismatch and disparity in MHC surface antigens are well-known to influence outcomes of transplanted tissues resulting in their use as predictors for allograft survival. (31)(32)(33) In liver transplantation, however, positive cross-matches appear more relevant than MHC or even ABO compatibility, highlighting the organ's tolerogenic properties. (34) Despite this behavior in solid organ transplantation, our experiments with different allogeneic responder PBMCs in coculture with the same PHHs or vice versa led to broad variation of proliferative outcomes, although correlation with the degree of HLA matching was still not observed.…”

Section: Discussionmentioning

confidence: 99%

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Hepatocyte‐induced CD4+ T cell alloresponse is associated with major histocompatibility complex class II up‐regulation on hepatocytes and suppressible by regulatory T cells

et al. 2018

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Hepatocyte transplantation is a promising therapeutic approach for various liver diseases. Despite the liver's tolerogenic potential, early immune‐mediated loss of transplanted cells is observed, and longterm acceptance has not been achieved yet. Patients deemed tolerant after liver transplantation presented an increased frequency of regulatory T cells (Tregs), which therefore also might enable reduction of posttransplant cell loss and enhance longterm allograft acceptance. We hence characterized hepatocyte‐induced immune reactions and evaluated the immunomodulatory potential of Tregs applying mixed lymphocyte cultures and mixed lymphocyte hepatocyte cultures. These were set up using peripheral blood mononuclear cells and primary human hepatocytes, respectively. Polyclonally expanded CD4+CD25highCD127low Tregs were added to cocultures in single‐/trans‐well setups with/without supplementation of anti‐interferon γ (IFNγ) antibodies. Hepatocyte‐induced alloresponses were then analyzed by multicolor flow cytometry. Measurements indicated that T cell response upon stimulation was associated with IFNγ‐induced major histocompatibility complex (MHC) class II up‐regulation on hepatocytes and mediated by CD4+ T cells. An indirect route of antigen presentation could be ruled out by use of fragmented hepatocytes and culture supernatants of hepatocytes. Allospecific proliferation was accompanied by inflammatory cytokine secretion. CD8+ T cells showed early up‐regulation of CD69 despite lack of cell proliferation in the course of coculture. Supplementation of Tregs effectively abrogated hepatocyte‐induced alloresponses and was primarily cell contact dependent. In conclusion, human hepatocytes induce a CD4+ T cell alloresponse in vitro, which is associated with MHC class II up‐regulation on hepatocytes and is susceptible to suppression by Tregs. Liver Transplantation 24 407–419 2018 AASLD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hepatocyte‐induced CD4+ T cell alloresponse is associated with major histocompatibility complex class II up‐regulation on hepatocytes and suppressible by regulatory T cells

et al. 2018

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“…[3][4][5][6][7][8] Despite the use of such therapeutic methods, graft survival in ABO-incompatible organ transplantation is generally inferior compared with that in ABO-compatible transplantation because of the reappearance of anti-A/B Abs. 1,4,[9][10][11][12] The specific and persistent inhibition of anti-A/B Ab production might be necessary for completely preventing anti-A/B Ab-mediated rejection; however, a method for either elimination or suppression of B-cell clones responding to the A/B carbohydrates has not yet been established.…”

Section: Introductionmentioning

confidence: 99%

The persistent elimination of B cells responding to blood group A carbohydrates by synthetic group A carbohydrates and B-1 cell differentiation blockade: novel concept in preventing antibody-mediated rejection in ABO-incompatible transplantation

Irei

Ohdan

Zhou

et al. 2007

Blood

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We demonstrated a novel strategy for specific and persistent inhibition of antibody (Ab) production against blood group A or B carbohydrate determinants necessary for successful ABO-incompatible transplantation. Similar to human blood group O or B individuals, mice have naturally occurring Abs against human blood group A carbohydrates in their sera. B cells with receptors for A carbohydrates in mice belonging to the CD5+CD11b+B-1a subset have phenotypic properties similar to those of human B cells. These cells could be temporarily eliminated by injecting synthetic A carbohydrates (GalNAcα1–3, Fucα1–2Gal) conjugated to bovine serum albumin (A-BSA) and anti-BSA Abs. In mice that received the injection of A-BSA/anti-BSA Abs, the serum levels of anti-A IgM were reduced, but immunization with human A erythrocytes resulted in increased serum levels of anti-A Abs. When combined with cyclosporin A (CsA) treatment, which blocks B-1a cell differentiation, and treatment with A-BSA/anti-BSA Abs, the serum levels of anti-A Abs were persistently undetectable in the mice even after the immunization. B cells with receptors for A carbohydrates were markedly reduced in these mice. These results are consistent with the hypotheses that treatment with A-BSA/anti-BSA Abs temporarily depletes B cells responding to A determinants, and CsA treatment prevents the replenishment of these cells.

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