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

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.

scholarly journals Importance of immunoglobulin isotype in human antibody-dependent, cell-mediated cytotoxicity directed by murine monoclonal antibodies.

1985 ◽  
Vol 161 (1) ◽  
pp. 1-17 ◽  
Author(s):  
T J Kipps ◽  
P Parham ◽  
J Punt ◽  
L A Herzenberg
Keyword(s):  
Human Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Cytolytic Activity ◽  
Human Antibody ◽  
Adcc Activity ◽  
Effector Cells ◽  
K Cells ◽  
Dependent Cell ◽  
Switch Variant ◽  
Murine Monoclonal Antibodies

Using the fluorescence activated cell sorter to select rare IgG2a- and IgG2b-producing variants, we developed switch variant families of hybridomas from IgG1-producing hybridomas, ME1 and MA2.1. The IgG2a and IgG2b antibodies produced by such switch variants have the same binding activities for HLA as the IgG1 antibodies produced by the parent hybridomas. Using these antibodies, we directly compared the IgG1, IgG2a, and IgG2b murine Ig isotypes for their capacities to direct human peripheral blood lymphocytes (PBL) in antibody-dependent cell-mediated cytotoxicity (ADCC) against a B lymphoblastoid cell line. We demonstrate that, for antibodies of identical binding affinity and specificity, the murine IgG2a isotype is the most effective in directing ADCC by human effector cells. The murine IgG2b directs intermediate levels of ADCC activity while IgG1 is inactive. We identified the effector cells in human PBL that mediate IgG2a or IgG2b ADCC as nonadherent killer (K) cells. These cells express the C3bi receptor and have cytolytic activity which is specifically blocked by a monoclonal antibody (anti-Leu-11a) that binds the Fc receptor (FcR) of such cells. Finally, FcR-bearing K cells bind to target cell-bound, rather than free, IgG2a or IgG2b molecules.

Morphological studies of bone and tendon

1992 ◽  
Vol 73 (2) ◽  
pp. S10-S13 ◽  
Author(s):  
S. B. Doty ◽  
E. R. Morey-Holton ◽  
G. N. Durnova ◽  
A. S. Kaplansky
Keyword(s):  
Electron Microscopy ◽  
Bone Cells ◽  
Weight Bearing ◽  
Light And Electron Microscopy ◽  
Cell Activity ◽  
Bone Cell ◽  
Electron Microscopic ◽  
Adult Rats ◽  
Morphological Studies ◽  
Metatarsal Bones

The Soviet biosatellite COSMOS 2044 carried adult rats on a spaceflight that lasted 13.8 days and was intended to repeat animal studies carried out on COSMOS 1887. Skeletal tissue and tendon from animals flown on COSMOS 2044 were studied by light and electron microscopy, histochemistry, and morphometric techniques. Studies were confined to the bone cells and vasculature from the weight-bearing tibias. Results indicated that vascular changes at the periosteal and subperiosteal region of the tibia were not apparent by light microscopy or histochemistry. However, electron microscopy indicated that vascular inclusions were present in bone samples from the flight animals. A unique combination of microscopy and histochemical techniques indicated that the endosteal osteoblasts from this same mid-diaphyseal region demonstrated a slight (but not statistically significant) reduction in bone cell activity. Electron-microscopic studies of the tendons from metatarsal bones showed a collagen fibril disorganization as a result of spaceflight. Thus changes described for COSMOS 1887 were present in COSMOS 2044, but the changes ascribed to spaceflight were not as evident.

scholarly journals HLA restriction of human cytotoxic T lymphocytes specific for influenza virus. Poor recognition of virus associated with HLA A2.

1978 ◽  
Vol 148 (6) ◽  
pp. 1458-1467 ◽  
Author(s):  
A McMichael
Keyword(s):  
Influenza Virus ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Influenza A ◽  
Human Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
The Other ◽  
Target Cells ◽  
Surface Molecules ◽  
Human Peripheral Blood Lymphocytes

Cytotoxic T lymphocytes (CTL), specific for influenza A/X31 virus, were generated from human peripheral blood lymphocytes. These CTL lysed target cells that were infected with the same virus and that shared HLA A or B locus antigens. Minimal lysis was observed when HLA-D antigens were shared. Not all HLA A and B antigens were equally effective. Efficient lysis of target cells was seen when HLA A1, A3, B7, B8, B27 and BW21 were shared with the CTL, but when HLA A2 was the only shared antigen lysis was usually minimal. This deficiency in CTL function associated with HLA A2 was not absolute. It is suggested that the function of this antigen might be influenced by other surface molecules on the cell and in particular the other HLA products.

Human neutrophil – mediated destruction of antibody sensitized herpes simplex virus type I infected cells

1978 ◽  
Vol 24 (2) ◽  
pp. 182-186 ◽  
Author(s):  
Yoshaiki Fujimiya ◽  
Barry T. Rouse ◽  
Lorne A. Babiuk
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Human Peripheral Blood ◽  
Polymorphonuclear Neutrophils ◽  
Target Cells ◽  
Type I ◽  
Effector Cells ◽  
Ability To Act ◽  
Simplex Virus

Human peripheral blood polymorphonuclear neutrophils (PMN) were tested for their ability to act as effector cells in antibody-dependent cell cytotoxicity (ADCC) against Herpes simplex virus (HSV) infected target cells sensitized with anti-HSV serum. The PMN from all 29 individuals tested could mediate ADCC in the presence of a standard human anti-HSV serum. Since PMN are prominent cells early in herpes lesions, it was hypothesized that because ADCC could represent an in vitro model for antiviral recovery, perhaps the efficacy of PMN at mediating ADCC might be impaired in those subject to frequent recrudescent herpes. However, evidence for the hypothesis was not obtained since the PMN from individuals with frequent, infrequent, or unrecorded herpes labialis all showed approximately the same activity at mediating ADCC. Alternative ways in which PMN could be involved in antiviral recovery were discussed.

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

PEDIATRICS ◽  
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.

Fas-based d1OS-mediated cytotoxicity requires macromolecular synthesis for effector cell activation but not for target cell death

1994 ◽  
Vol 345 (1313) ◽  
pp. 303-309 ◽  
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Cell Surface ◽  
Target Cell ◽  
Cell Activation ◽  
Effector Cell ◽  
Apoptotic Cell ◽  
Target Cells ◽  
Macromolecular Synthesis ◽  
Effector Cells

Two main mechanisms seem at play in T cell-mediated cytotoxicity, a process in which target cell death often follows an apoptotic cell death pattern. One of these involves Fas at the target cell surface and a Fas ligand at the effector cell surface. This allowed us to reinvestigate the long-standing question of macromolecular synthesis requirement in T cell-mediated cytotoxicity, using the dlOS model cell line which is cytotoxic apparently only via the Fas molecularly defined mechanism. We showed, first, that induction of cytotoxic activity of effector cells, obtained by preincubating these effector cells with a phorbol ester and a calcium ionophore, could be inhibited by macromolecular synthesis inhibitors (cycloheximide, actinomycin D, DRB). We then investigated whether macromolecular synthesis was required, when effector and target cells were mixed, to obtain target cell death. Preincubating already activated effector cells for 30 min with macromolecular synthesis inhibitors, then adding target cells and performing the 51 Cr release cytotoxicity test in the presence of these inhibitors, did not significantly decrease subsequent target cell death, indicating that already activated effector cells could kill without further requirement for macromolecular synthesis. In addition, target cell preincubation for up to 3 h in the presence of one of these inhibitors did not decrease cell death. The high sensitivity of mouse thymocytes to this type of cytotoxicity enabled us to devise the following experiment. As previously shown by others, thymocyte death induced by dexamethasone (DEX) could be blocked by coincubation with cycloheximide (CHX). Such DEX-treated CHX-rescued thymocytes, the survival of which was an internal control of efficiency of protein synthesis inhibition, were then subjected to effector cells in the presence of CHX, and were shown to die. Thus, there is no requirement for macromolecular synthesis at the target cell level in this variety of apoptotic cell death. Altogether, in this defined mechanism of T cell-mediated cytotoxicity, macromolecular synthesis is required for dlOS effector cell activation, but not for lysis by already activated effector cells nor for target cell death.

Sign in / Sign up

Export Citation Format

Share Document