Antibody mediated lysis of hapten-conjugated target cells by macrophages and by complement: The influence of IgG subclass, antibody and hapten density

Miklós, Kata; Tolnay, Máté; Bazin, Hervé; Medgyesi, G

doi:10.1016/0161-5890(92)90025-s

Cited by 17 publications

(9 citation statements)

References 23 publications

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“…The amount of bound non-␣Gal Ab required to induce complement lysis was rather high compared with ADCC. This finding correlates with an earlier study indicating that the threshold for NAb/complement-induced cytotoxicity may be higher than the threshold to induce ADCC (59).…”

Section: Discussionsupporting

confidence: 81%

Lack of Galactose-α-1,3-Galactose Expression on Porcine Endothelial Cells Prevents Complement-Induced Lysis but Not Direct Xenogeneic NK Cytotoxicity

Baumann

Forte

Hawley³

et al. 2004

The Journal of Immunology

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The galactose-α-1,3-galactose (αGal) carbohydrate epitope is expressed on porcine, but not human cells, and therefore represents a major target for preformed human anti-pig natural Abs (NAb). Based on results from pig-to-primate animal models, NAb binding to porcine endothelial cells will likely induce complement activation, lysis, and hyperacute rejection in pig-to-human xenotransplantation. Human NK cells may also contribute to innate immune responses against xenografts, either by direct recognition of activating molecules on target cells or by FcγRIII-mediated xenogeneic Ab-dependent cellular cytotoxicity (ADCC). The present study addressed the question as to whether the lack of αGal protects porcine endothelial cells from NAb/complement-induced lysis, direct xenogeneic NK lysis, NAb-dependent ADCC, and adhesion of human NK cells under shear stress. Homologous recombination, panning, and limiting dilution cloning were used to generate an αGal-negative porcine endothelial cell line, PED2*3.51. NAb/complement-induced xenogeneic lysis of PED2*3.51 was reduced by an average of 86% compared with the αGal-positive phenotype. PED2*3.51 resisted NK cell-mediated ADCC with a reduction of lysis ranging from 30 to 70%. However, direct xenogeneic lysis of PED2*3.51, mediated either by freshly isolated or IL-2-activated human NK cells or the NK cell line NK92, was not reduced. Furthermore, adhesion of IL-2-activated human NK cells did not rely on αGal expression. In conclusion, removal of αGal leads to a clear reduction in complement-induced lysis and ADCC, but does not resolve adhesion of NK cells and direct anti-porcine NK cytotoxicity, indicating that αGal is not a dominant target for direct human NK cytotoxicity against porcine cells.

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Section: Discussionsupporting

confidence: 81%

Lack of Galactose-α-1,3-Galactose Expression on Porcine Endothelial Cells Prevents Complement-Induced Lysis but Not Direct Xenogeneic NK Cytotoxicity

Baumann

Forte

Hawley³

et al. 2004

The Journal of Immunology

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“…Experiments to determine the role in vivo of Th2 cytokines used the following antibodies: anti-IL-4 mAb, 11B11 [rIgGl; (18)], anti-IL-10 mAb, JES5-2A5 [rIgGl; (19)], or a control isotype-matched mAb, LO-DNP-2 [rIgGl; (20)]. …”

Section: Monoclonal Antibodies 3 Resultsmentioning

confidence: 99%

A role for Th2 cytokines in the suppression of CD8⁺ T cell‐mediated graft rejection

et al. 1997

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A major histocompatibility complex (MHC) class I-specific T cell receptor (TCR)-transgenic mouse was used to study classical-type transplantation tolerance in the adult. Engraftment of MHC class I-incompatible bone marrow and tolerance to donor-type skin grafts were obtained using dimethylmyeleran (DMM) as a myeloablative agent and a non-depleting anti-CD8 monoclonal antibody (mAb) as the sole immunosuppressant. Surprisingly, bone marrow engraftment was facilitated by host CD4+ T cells, a subset normally considered unable to reject class I MHC-incompatible grafts. A combination of mAb to interleukins (IL)-4 and -10 antagonized the "permissive" effects of host CD4+ T cells, indicating a possible role for Th2-type immunoregulation that can act on CD8+ T cells in this form of transplantation tolerance. The fate of graft-reactive T cells was monitored using anti-clonotypic antibodies. It was observed that bone marrow engraftment then led to peripheral deletion of mAb-blockaded, clonotype+ CD8+ T cells.

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“…4B) in vitro. This is in keeping with the activity of rat IgG2b in fixing complement (37) and the ability of IgG2a and IgG2b to bind to the Fc receptor (58,59). Both IgG subclasses are also likely to participate in promoting graft rejection in vivo.…”

Section: Discussionmentioning

confidence: 88%

“…In this presensitized model, accommodation occurs in association with the longest delay and lowest rate of return of anti-graft Ab titers. Given the capacity of the rat IgG subclasses in mediating CDC (IgG2a and IgG2b) and ADCC (IgG1, IgG2a, and IgG2b) (37,58,59), the lack of IgG1 as well as the decrease in IgG2a and IgG2b may facilitate the development of accommodation. However, it is uncertain whether the lack of IgG1 is specifically required for accommodation.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Survival of Hamster Hearts in Presensitized Rats

Lin

Soares

Sato

et al. 2000

The Journal of Immunology

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We transplanted hamster hearts into rats that had been sensitized to hamster cardiac grafts 5 days earlier as a model for discordant xenotransplantation. Sensitized rats had high serum levels of elicited anti-donor IgM and IgG that caused hyperacute rejection. Transient complement inhibition with cobra venom factor (CVF) plus daily and continuing cyclosporin A (CyA) prevented hyperacute rejection. However, grafts underwent delayed xenograft rejection (DXR). DXR involved IgG and associated Ab-dependent cell-mediated rejection, because depletion of IgG or Ab-dependent cell-mediated rejection-associated effector cells prolonged graft survival and the serum-mediated Ab-dependent cell-mediated cytotoxicity in vitro. Blood exchange in combination with CVF/CyA treatment dramatically decreased the level of preexisting Abs, but DXR still occurred in association with the return of Abs. Splenectomy and cyclophosphamide acted synergistically to delay Ab return, and when combined with blood exchange/CVF/CyA facilitated long-term survival of grafts. These grafts survived in the presence of anti-donor IgM, IgG, and complement that precipitated rejection of naive hearts, indicating that accommodation (survival in the presence of anti-graft Abs and complement) had occurred. We attribute the long-term survival to the removal of preexisting anti-donor Abs and therapy that attenuated the rate of Ab return. Under such conditions, the surviving hearts showed expression in endothelial cells and smooth muscle cells of protective genes and an intragraft Th2 immune response. Th2 responses and protective genes are associated with resistance to IgM- and IgG-mediated, complement-dependent and -independent forms of rejection.

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Antibody mediated lysis of hapten-conjugated target cells by macrophages and by complement: The influence of IgG subclass, antibody and hapten density

Cited by 17 publications

References 23 publications

Lack of Galactose-α-1,3-Galactose Expression on Porcine Endothelial Cells Prevents Complement-Induced Lysis but Not Direct Xenogeneic NK Cytotoxicity

Lack of Galactose-α-1,3-Galactose Expression on Porcine Endothelial Cells Prevents Complement-Induced Lysis but Not Direct Xenogeneic NK Cytotoxicity

A role for Th2 cytokines in the suppression of CD8⁺ T cell‐mediated graft rejection

Long-Term Survival of Hamster Hearts in Presensitized Rats

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Antibody mediated lysis of hapten-conjugated target cells by macrophages and by complement: The influence of IgG subclass, antibody and hapten density

Cited by 17 publications

References 23 publications

Lack of Galactose-α-1,3-Galactose Expression on Porcine Endothelial Cells Prevents Complement-Induced Lysis but Not Direct Xenogeneic NK Cytotoxicity

Lack of Galactose-α-1,3-Galactose Expression on Porcine Endothelial Cells Prevents Complement-Induced Lysis but Not Direct Xenogeneic NK Cytotoxicity

A role for Th2 cytokines in the suppression of CD8+ T cell‐mediated graft rejection

Long-Term Survival of Hamster Hearts in Presensitized Rats

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A role for Th2 cytokines in the suppression of CD8⁺ T cell‐mediated graft rejection