Antibody-dependent cell-mediated cytotoxicity in cows: comparison of effector cell activity against heterologous erthrocyte and herpesvirus-infected bovine target cells.

Acute kidney injury (AKI) and nephrotic syndrome (NS) are uncommon manifestations of Epstein-Barr virus (EBV) mononucleosis. We report a 4-year-old boy with Infectious mononucleosis (IM) who presented with dialysis-requiring AKI and NS. Renal biopsy showed severe acute tubular necrosis, mild chronic interstitial nephritis and focal podocyte foot processes effacement. EBV early RNA was not detected in the renal tissue. However, immunophenotyping of peripheral lymphocytes showed increased cytotoxic T cell activity and increased memory B cells. Treatment with steroid led to rapid resolution of NS within 3 weeks. Renal function stabilised. EBV viral capsid antigen (VCA) IgM remained elevated until 4 months before starting to decline when VCA IgG and nuclear antigen started appearing. B lymphocytes are the predominant target cells in EBV infection and additionally may also act as antigen presenting cells to T lymphocytes, thereby eliciting the strong immune response and leading to podocyte and tubulointerstitial injury.

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Interactions between Effector Cell Activity and Lymphokines: Implications for Recovery from Herpesvirus Infections

International Archives of Allergy and Immunology ◽

10.1159/000232085 ◽

1978 ◽

Vol 57 (1) ◽

pp. 62-73 ◽

Cited By ~ 9

Author(s):

Lorne A. Babiuk ◽

Barry T. Rouse

Keyword(s):

Effector Cell ◽

Cell Activity

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FcαRI (CD89) as a Novel Trigger Molecule for Bispecific Antibody Therapy

Blood ◽

10.1182/blood.v90.11.4485.4485_4485_4492 ◽

1997 ◽

Vol 90 (11) ◽

pp. 4485-4492 ◽

Cited By ~ 3

Author(s):

Thomas Valerius ◽

Bernhard Stockmeyer ◽

Annemiek B. van Spriel ◽

Robert F. Graziano ◽

Ingrid E. van den Herik-Oudijk ◽

...

Keyword(s):

Tumor Cell ◽

Whole Blood ◽

Effector Cell ◽

Bispecific Antibody ◽

Fc Receptor ◽

Bispecific Antibodies ◽

Target Cells ◽

Antibody Isotype ◽

Her 2 ◽

Trigger Molecule

Promising results from clinical trials with unconjugated antibodies stimulated renewed interest in immune effector mechanisms of monoclonal antibodies (MoAbs). We investigated the potential of IgA as antibody isotype for cell- or complement-mediated tumor cell lysis and assessed the potential of its myeloid Fc receptor, FcαRI (CD89), as trigger molecule for bispecific antibody (BsAb)-mediated immunotherapy. Comparing hapten-directed antibodies of human IgA2 with IgG1 or IgG3 isotypes, we found all three to mediate effective killing of sensitized tumor target cells in whole blood assays. Analysis of effector mechanisms showed IgG-mediated lysis to be predominantly complement-dependent, whereas IgA-dependent killing was primarily effector cell-mediated. A comparison of effector cell populations in antibody-dependent cell-mediated cytotoxicity (ADCC) showed neutrophils to be most important for IgA-dependent tumor cell killing, involving FcαRI as shown with Fc receptor blocking antibodies. Reverse ADCC experiments against target cells sensitized with Fc receptor antibodies, or assays with FcαRI-directed bispecific antibodies confirmed FcαRI as effective trigger molecule in polymorphonuclear neutrophil (PMN)-mediated lysis. During granulocyte colony-stimulating factor (G-CSF ) therapy, (FcαRI × HER-2/neu) bispecific antibodies induced enhanced killing of HER-2/neu positive SK-BR–3 breast cancer cells in whole blood assays. This enhanced cytotoxicity was paralleled by increased PMN counts, which lead to higher effector to target cell ratios in G-CSF–primed blood. Furthermore, bispecific antibodies, directed to FcαRI and Candida albicans, enhanced neutrophils' phagocytosis of fungi. In summary, these results identify IgA as an effective antibody isotype for immunotherapy, working primarily via FcαRI on neutrophils. They suggest FcαRI-directed bispecific antibodies and G-CSF to be an attractive combination for malignant or infectious diseases.

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Antibody-Dependent Cellular Cytotoxicity to Target Cells Infected With Herpes Simplex Viruses: Functional Adequacy in the Neonate

PEDIATRICS ◽

10.1542/peds.59.1.22 ◽

1977 ◽

Vol 59 (1) ◽

pp. 22-28

Author(s):

Steven L. Shore ◽

Henry Milgrom ◽

Phyllis A. Wood ◽

André J. Nahmias

Keyword(s):

Herpes Simplex ◽

Cord Blood ◽

Mononuclear Cells ◽

Cell Activity ◽

Absolute Number ◽

Target Cells ◽

Cellular Cytotoxicity ◽

Antibody Dependent Cellular Cytotoxicity ◽

Effector Cells ◽

Herpes Simplex Viruses

The functional adequacy of antibody-dependent cellular cytotoxicity (ADCC) in the human neonate was evaluated in a 51Cr release assay which employs tissue culture cells acutely infected with type 1 or type 2 herpes simplex virus (HSV) as targets. Two aspects of ADCC were assessed: cytotoxic effector activity in cord blood mononuclear cells (MC) and the ability of the antibody mediating ADCC to pass the placenta. Although effector cell activity was readily detected in all 13 cord blood specimens tested, cord blood MC showed moderately reduced cytotoxic activity when compared with blood MC from normal adults at the same effector cell:target cell ratio. This finding suggests that effector cells in cord blood make up a reduced proportion of the total circulating MC population and may be of relevance to the newborns increased susceptibility to HSV infection. On the other hand, the number of MC in cord blood was found to be almost twice that of adult blood, suggesting that the absolute number of ADCC effector cells in cord blood was within the adult range. The antibody mediating ADCC to HSV-infected cells was shown to be transferred (quantitatively across the placenta, providing further evidence that it is an IgG immunoglobulin.

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Apoptosis as the mode of cell death in antibody-dependent lymphocytotoxicity

Journal of Cell Science ◽

10.1242/jcs.74.1.169 ◽

1985 ◽

Vol 74 (1) ◽

pp. 169-179

Author(s):

N.H. Stacey ◽

C.J. Bishop ◽

J.W. Halliday ◽

W.J. Halliday ◽

W.G. Cooksley ◽

...

Keyword(s):

Cell Death ◽

Human Peripheral Blood ◽

Cell Activity ◽

Peripheral Blood Lymphocytes ◽

Cell Killing ◽

Target Cells ◽

Human Antibody ◽

Electron Microscopic ◽

Effector Cells ◽

Morphological Studies

A light and electron microscopic study of antibody-dependent lymphocytotoxicity was carried out with the object of elucidating the mechanisms responsible for the cell killing, the basis for the research being the relationship that has recently been shown to exist between the morphology of cell death and its pathogenesis. Chang liver cells coated with a rabbit anti-human antibody were used as targets and normal human peripheral-blood lymphocytes as effector cells. Cytotoxicity assays using release of 51Cr demonstrated extensive K-cell killing, thus validating the suitability of the model for morphological studies. Cell death displaying the features of apoptosis correlated with K-cell activity. A small amount of cell death by classical necrosis was observed, but its extent appeared to be unrelated to the presence of lymphocytes, to pre-treatment of the target cells with antibody, or to the magnitude of 51Cr release. The results support evidence indicating that lymphocytotoxicity depends on activation of a self-destruct program within the target cell. They do not favour a mechanism involving the production of plasma membrane lesions analogous to those responsible for complement-mediated immune cytolysis.

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The Contribution of IgG Glycosylation to Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Complement-Dependent Cytotoxicity (CDC) in Hashimoto’s Thyroiditis: An in Vitro Model of Thyroid Autoimmunity

Biomolecules ◽

10.3390/biom10020171 ◽

2020 ◽

Vol 10 (2) ◽

pp. 171 ◽

Cited By ~ 1

Author(s):

Marta Ząbczyńska ◽

Katarzyna Polak ◽

Kamila Kozłowska ◽

Grzegorz Sokołowski ◽

Ewa Pocheć

Keyword(s):

Cell Line ◽

Hashimoto’S Thyroiditis ◽

Leukemia Cell Line ◽

Hashimoto's Thyroiditis ◽

Target Cells ◽

Healthy Donors ◽

Complement Dependent Cytotoxicity ◽

Dependent Cell ◽

Igg Glycosylation

Antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) are involved in destruction of thyroid tissue in Hashimoto’s thyroiditis (HT). N-glycosylation of the Fc fragment affects the effector functions of IgG by enhancing or suppressing the cytotoxicity effect. The aim of the present study was to assess the impact of HT-specific IgG glycosylation in ADCC and CDC, using in vitro models. The normal thyroid Nthy-ori 3-1 cell line and thyroid carcinoma FTC-133 cells were used as the target cells. Peripheral blood mononuclear cells (PBMCs) from healthy donors and the HL-60 human promyelotic leukemia cell line served as the effector cells. IgG was isolated from sera of HT and healthy donors and then treated with α2-3,6,8-neuraminidase to cut off sialic acids (SA) from N-glycans. We observed more intensive cytotoxicity in the presence of IgG from HT patients than in the presence of IgG from healthy donors. Removal of SA from IgG N-glycans increased ADCC intensity and reduced CDC. We conclude that the enhanced thyrocyte lysis resulted from the higher anti-TPO content in the whole IgG pool of HT donors and from altered IgG glycosylation in HT autoimmunity.

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Thermal stresses reduce natural killer cell cytotoxicity

Journal of Applied Physiology ◽

10.1152/jappl.1995.79.3.732 ◽

1995 ◽

Vol 79 (3) ◽

pp. 732-737 ◽

Cited By ~ 29

Author(s):

S. J. Won ◽

M. T. Lin

Keyword(s):

Nk Cells ◽

Natural Killer ◽

Target Cell ◽

Nk Cell ◽

Cell Activity ◽

Cortisol Concentration ◽

Target Cells ◽

Nk Cell Activity ◽

Colonic Temperature ◽

Effector Target

The effects of different ambient temperatures (Ta) on the splenic natural killer (NK) cell activity, effector-target cell conjugation activity, and NK cell numbers were assessed in male inbred C3H/HeNCrj mice (7–10 wk old). The splenic NK cytotoxic activities were examined in a 4-h 51Cr release assay in mouse spleen cells that were obtained 1, 2, 4, 8, or 16 days after exposure to Ta of 22, 4, or 35 degrees C. The percentage of conjugating lymphocytes was calculated by counting the number of single lymphocytes bound to single target cells per 400 effector cells. The numbers of NK cells were expressed by the percentage of 5E6-positive cells. The 5E6 identifies only a subset of NK cells. It was found that the splenic NK cell activity, the effector-target cell conjugation activity, or the NK cell number began to fall 1 day after cold (Ta 4 degrees C) or heat (Ta 35 degrees C) stress. After a 16-day period of either cold or heat exposure, the fall in the splenic NK cell activity, the effector-target cell conjugation activity, or the number of 5E6-positive subsets of NK cells was still evident. Compared with those of the control group (Ta 22 degrees C), the cold-stressed mice had higher adrenal cortisol concentration and lower colonic temperature, whereas the heat-stressed animals had higher adrenal cortisol concentration and higher colonic temperature during a 16-day period of thermal exposure. However, neither cold nor heat stress affected both the body weight gain and the spleen weight in our mice.

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