scholarly journals Antiphosphatidylserine antibodies in human immunodeficiency virus-1 patients with evidence of T-cell apoptosis and mediate antibody- dependent cellular cytotoxicity [see comments]

Blood ◽  
1996 ◽  
Vol 87 (12) ◽  
pp. 5185-5195 ◽  
Author(s):  
F Silvestris ◽  
MA Frassanito ◽  
P Cafforio ◽  
D Potenza ◽  
M Di Loreto ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Cell Apoptosis ◽  
Clinical Feature ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cellular Cytotoxicity ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
T Cell Apoptosis ◽  
Immunodeficiency Virus ◽  
Hiv 1

Serum reactivities to a panel of phospholipid antigens, including cardiolipin (CL), phosphatidylserine (PS), sphingomyelin, phosphatidylcholine, and phosphatidylethanolamine, were measured by enzyme-linked immunosorbent assay in 196 human immunodeficiency virus- l+ (HIV-1+) patients with CDC II to IVC clinical disease. Significant levels of IgG to CL, PS, or both were observed in 23 patients lacking evidence of thrombophilic events or any peculiar clinical feature of HIV-1 infection. Fluorescence-activated cell sorting analyses showed that in vitro apoptosis of T cells was increased in patients with high serum anti-PS IgG, whereas the overexpression of Fas/Apo-1 marker was detected in all patients regardless of their antiphospholipid reactivities. Macrophages from patients with significant titers of anti- PS IgG antibodies were not activated by the presence of apoptotic CEM lymphoblasts or by purified anti-PS IgG from the same patients. By contrast, these antibodies greatly improved the effector functions of autologous macrophages in antibody-dependent cellular cytotoxicity (ADCC) assays using 51Cr-labeled CEM cells, whereas polyspecific IgG were unable to induce an equivalent cytotoxicity in all instances. An increasing effect on ADCC was also observed in tests using macrophages from healthy controls to CEM coated with anti-PS IgG. These results support a potential correlation of anti-PS specificity with T-cell apoptosis in HIV-1 infection. Because PS is exteriorized by apoptotic lymphocytes, its persistence may stimulate antibodies which cooperate with macrophages in the clearance of dead cells by an enhanced ADCC mechanism. This interpretation could explain the absence of thrombophilia in HIV-1+ patients with serum elevations of antiphospholipid reactivities.

scholarly journals Loss of CD4+ T Cells in Human Immunodeficiency Virus Type 1-Infected Chimpanzees Is Associated with Increased Lymphocyte Apoptosis

1998 ◽  
Vol 72 (6) ◽  
pp. 4623-4632 ◽  
Author(s):  
Ian C. Davis ◽  
Marc Girard ◽  
Patricia N. Fultz
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Human Immunodeficiency Virus Type ◽  
Cell Apoptosis ◽  
T Cell Apoptosis ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Supportive evidence that apoptosis contributes to loss of CD4+ lymphocytes in human immunodeficiency virus type 1 (HIV-1)-infected humans comes from an apparent lack of abnormal apoptosis in apathogenic lentivirus infections of nonhuman primates, including HIV-1 infection of chimpanzees. Two female chimpanzees were inoculated, one cervically and the other intravenously, with HIV-1 derived from the LAI/LAV-1b strain, which was isolated from a chimpanzee infected with the virus for 8 years. Within 6 weeks of infection, both recipient chimpanzees developed a progressive loss of CD4+ T cells which correlated with persistently high viral burdens and increased levels of CD4+ T-cell apoptosis both in vitro and in vivo. Lymph nodes from both animals also revealed evidence of immune hyperactivation. Intermediate levels of T-cell apoptosis in both peripheral blood and lymph nodes were seen in a third chimpanzee that had been infected with the LAI/LAV-1b strain for 9 years; this animal has maintained depressed CD4/CD8 T-cell ratios for the last 3 years. Similar analyses of cells from 4 uninfected animals and 10 other HIV-1-infected chimpanzees without loss of CD4+ cells revealed no difference in levels of apoptosis in these two control groups. These results demonstrate a correlation between immune hyperactivation, T-cell apoptosis, and chronic loss of CD4+ T cells in HIV-1-infected chimpanzees, providing additional evidence that apoptosis is an important factor in T-cell loss in AIDS. Furthermore, the results show that some HIV-1 strains are pathogenic for chimpanzees and that this species is not inherently resistant to HIV-1-induced disease.

scholarly journals Antibody-Dependent Cellular Cytotoxicity Directed against Cells Expressing Human Immunodeficiency Virus Type 1 Envelope of Primary or Laboratory-Adapted Strains by Human and Chimpanzee Monoclonal Antibodies of Different Epitope Specificities

1998 ◽  
Vol 72 (1) ◽  
pp. 286-293 ◽  
Author(s):  
Osama Alsmadi ◽  
Shermaine A. Tilley
Keyword(s):  
Human Immunodeficiency Virus ◽  
Monoclonal Antibodies ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cellular Cytotoxicity ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Adcc Activity ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The characteristics of antibody-dependent cellular cytotoxicity (ADCC) directed by a panel of human and chimpanzee antienvelope (anti-Env) monoclonal antibodies (MAbs) of different epitope specificities were studied; this was accomplished by using target cells expressing human immunodeficiency virus type 1 (HIV-1) Envs of either primary or laboratory-adapted strains. Human MAbs of similar apparent affinities (1 × 109 to 2 × 109 liters/mol) against either a “cluster II”-overlapping epitope of gp41 or against the CD4 binding site, V3 loop, or C5 domain of gp120 directed substantial and comparable levels of specific lysis against targets infected with laboratory-adapted strains of HIV-1. As expected, those MAbs specific for relatively conserved regions of Env generally exhibited ADCC activity against a broader range of HIV-1 strains than those directed against variable epitopes. Significant ADCC activities of selected MAbs against primary isolate Env-expressing cells were demonstrated. In addition, a new ADCC epitope in the V2 domain of gp120 was defined. CD56+ cells were demonstrated to be the effector cells in these studies by fluorescence-activated cell sorting followed by ADCC assays. Notably, all anti-Env MAbs tested in this study, including MAbs directed against each of the known neutralization epitope clusters in gp120, directed significant levels of ADCC against targets expressing Env of one or more HIV-1 strains. These results imply that many, if not most, HIV-1-neutralizing human Abs of high affinity (≥3 × 108 liters/mol in these studies) and of the immunoglobulin G1 (IgG1) subclass (i.e., the predominate IgG subclass) are capable of directing ADCC. Since neutralizing Abs have been associated with long-term survival following HIV-1 infection, this suggests that ADCC activity may be beneficial in vivo.

scholarly journals T-Cell Apoptosis in Inflammatory Neuromuscular Disorders Associated With Human Immunodeficiency Virus Infection

1999 ◽  
Vol 56 (1) ◽  
pp. 79 ◽  
Author(s):  
Christiane Schneider ◽  
Marinos C. Dalakas ◽  
Klaus V. Toyka ◽  
Gérard Said ◽  
Hans-Peter Hartung ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Virus Infection ◽  
Human Immunodeficiency Virus Infection ◽  
Cell Apoptosis ◽  
Neuromuscular Disorders ◽  
T Cell Apoptosis ◽  
Immunodeficiency Virus

scholarly journals A Cysteine Protease Inhibitor Prevents Activation-Induced T-Cell Apoptosis and Death of Peripheral Blood Cells From Human Immunodeficiency Virus-Infected Individuals by Inhibiting Upregulation of Fas Ligand

Blood ◽  
1997 ◽  
Vol 89 (2) ◽  
pp. 550-557 ◽  
Author(s):  
Yili Yang ◽  
Zhi-Hong Liu ◽  
Carl F. Ware ◽  
Jonathan D. Ashwell
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Death ◽  
T Cell ◽  
Protease Inhibitor ◽  
Cell Apoptosis ◽  
Fas Ligand ◽  
Cysteine Protease Inhibitor ◽  
Infected Blood ◽  
T Cell Apoptosis ◽  
Immunodeficiency Virus

Abstract Activation of T-cell hybridomas, preactivated normal T cells, and peripheral blood lymphocytes (PBL) from human immunodeficiency virus (HIV)-infected individuals results in apoptosis. In the first two cases, apoptosis is caused by the upregulation of Fas ligand (FasL) and its subsequent interaction with Fas; the mechanism for the spontaneous and activation-induced death of lymph node cells and PBL from HIV+ blood is not known. A number of protease inhibitors have been shown to prevent T-cell apoptosis under all of these circumstances, but the mechanism of action has not been determined. Here we show that the cysteine protease inhibitor E64d prevents activation-induced T hybridoma cell death by inhibiting the upregulation of FasL. Quantitative polymerase chain reaction (PCR) demonstrated that mRNA for FasL is expressed at low levels in fresh PBL from HIV-infected blood, but increases in cultured PBL from both uninfected and HIV-infected donors. The ex vivo apoptosis of PBL from HIV+ donors was prevented by adding the soluble extracellular domain of Fas, demonstrating a requisite role for Fas/FasL interactions in this form of cell death. Furthermore, while having no effect on the death of PBL from HIV-infected blood stimulated directly via Fas, E64d inhibited FasL upregulation. Thus, aberrant apoptosis of cultured PBL from HIV-infected individuals is mediated by FasL and Fas, and E64d blocks this apoptosis by inhibiting the upregulation of FasL. These results are consistent with the hypothesis that the abnormal expression of Fas and the inducible expression of FasL contributes to the immunodeficiency of patients with acquired immune deficiency syndrome and suggest that modulation of FasL expression could be an effective target for therapeutic intervention.

scholarly journals CXCR4-mediated T cell apoptosis in human immunodeficiency virus infection

2004 ◽  
Vol 85 (6) ◽  
pp. 1471-1478 ◽  
Author(s):  
Anne-Zélie Decrion ◽  
Audrey Varin ◽  
Jean-Marie Estavoyer ◽  
Georges Herbein
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
T Cell Activation ◽  
Cell Apoptosis ◽  
Mononuclear Cells ◽  
Viral Envelope ◽  
T Cell Apoptosis ◽  
Immunodeficiency Virus

Mechanisms of CXCR4-mediated T lymphocyte apoptosis in human immunodeficiency virus (HIV) infection are poorly understood. The authors used peripheral blood mononuclear cells isolated from HIV type 1-infected subjects and assessed both CD4+ and CD8+ T cell apoptosis in the presence and absence of CXCR4 blockade by AMD3100. Both CD4+ and CD8+ T cell apoptosis could be inhibited by CXCR4 blockade, mostly in acquired immunodeficiency syndrome subjects and more weakly in asymptomatic HIV-positive subjects, and depended only partially on the syncytium-inducing/non-syncytium-inducing viral envelope phenotype. Immune activation of CD8+, but not CD4+, T cells was CXCR4-dependent, resulting in increased T cell apoptosis. In the presence of monocyte-derived macrophages, CXCR4-mediated apoptosis targeted mostly CD8+ T cells, with CD4+ T cells being more weakly affected. Several immune and viral factors thus play a role in CXCR4-mediated T cell apoptosis in HIV infection: CD4/CD8 phenotype, viral envelope phenotype, T cell activation and T cell–macrophage intercellular contacts.

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