Induction of CD4<sup>+</sup> T cell depletion in mice doubly transgenic for HIV gp120 and human CD4

Finco, Oretta; Nuti, Sandra; Magistris, Maria Teresa De; Mangiavacchi, Lucia; Aiuti, Alessandro; Forte, Pietro; Fantoni, A; Putten, Herman van der; Abrignani, Sergio

doi:10.1002/eji.1830270604

Cited by 25 publications

(22 citation statements)

References 31 publications

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“…Interestingly, Chen et al (1994) reported that soluble HIV-1 gp41 enhanced ICAM-1 expression by 70% on monocytic cell line H9, but did not affect U937 cells, suggesting a selective biologic function of gp41 that is involved in the regulation of ICAM-1 expression. Moreover, a transgenic mouse model for HIV-1 gp120 has been established with secreted circulating levels of gp120 similar to those detected in AIDS patients (Finco et al, 1997), and significant up-regulation of ICAM-1 on brain endothelial cells has been found in this animal model (Toneatto et al, 1999). Thus, HIV-1 gp120 can directly increase ICAM-1 expression in several cell types, including endothelial cells, glial cells, and leukocytes.…”

mentioning

confidence: 83%

HIV-1 Envelope Glycoprotein 120 Increases Intercellular Adhesion Molecule-1 Expression by Human Endothelial Cells

Ren

Yao

Chen

2002

Laboratory Investigation

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SUMMARY:Human immunodeficiency virus type 1 (HIV-1) infection is often associated with central nervous system damage and vascular complications. However, the mechanisms of this association are largely unknown. We examined the effect of HIV-1 envelope glycoprotein 120 (gp120) on cell adhesion molecule expression by endothelial cells. We found, for the first time, that both soluble and membrane-bound gp120 could significantly increase the expression of human endothelial intercellular adhesion molecule-1 (ICAM-1) at both mRNA and protein levels, but not vascular cell adhesion molecule-1 and E-selectin. The specificity of gp120-mediated response was demonstrated by blocking experiments using a specific monoclonal antibody against gp120, which successfully abolished the gp120-mediated increase of ICAM-1 expression. Furthermore, there was a significant increase of human monocytic cell line THP-1 adherence onto the gp120-treated endothelial monolayers. This increased cell adhesion was effectively blocked by either anti-gp120 or anti-ICAM antibodies. These findings suggest that HIV-1 gp120-mediated endothelial ICAM-1 expression could be one of the important mechanisms of HIV-1 pathogenesis. (Lab Invest 2002, 82:245-255). B oth human immunodeficiency virus (HIV)-positiveand acquired immune deficiency syndrome (AIDS) patients often have significantly increased levels of circulating cell adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) (Greenwood et al, 1998; Seigneur et al, 1997). Serum ICAM-1 levels correlate well with AIDS progression in HIV type 1 (HIV-1)-infected patients (Galea et al, 1997). Endothelial cells and leukocytes from these patients exhibit a significant increase of such adhesion molecules (Pillet et al, 1999;Zietz et al, 1996). HIV-1 particles also incorporate many cell adhesion molecules (Guo and Hildreth, 1995). HIV-associated ICAM-1 is biologically active and can enhance virus infectivity (Fortin et al, 1997) and virus-induced syncytium formation (Gruber et al, 1991). ICAM-1-bearing viruses are less susceptible to neutralization by anti-envelope glycoprotein 120 (gp120) monoclonal antibodies than the same virus produced in cells expressing no ICAM-1 (Sawyer et al, 1994). HIV-1 replication in monocytes/macrophages is significantly enhanced by interaction with endothelial cells through cell adhesion molecules (Gilles et al, 1995). In addition, alterations in expression of cell adhesion molecules by leukocytes and endothelial cells can increase leukocyte migration into the tissues, which may result in certain organ damage. Indeed, HIV-1-infected leukocytes can transmigrate into the central nervous system and cause encephalopathy (Nottet, 1999). Endothelial cell dysfunction and leukocyte infiltration may also be attributable to the increased frequency of vascular complications such as atherosclerosis in HIV-1-infected patients (Constans et al, 1995;Tabib et al, 2000).Several factors may contribute to the increased levels of cell adhesion mole...

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confidence: 83%

HIV-1 Envelope Glycoprotein 120 Increases Intercellular Adhesion Molecule-1 Expression by Human Endothelial Cells

Ren

Yao

Chen

2002

Laboratory Investigation

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“…Antibody-mediated crosslinking of CD4 (or CXCR4) in the absence of CD3 stimulation can sensitize T lymphocytes to apoptosis induction, 32 and similar findings have been reported for the gp120-mediated activation of T cells. 33 Stimuli converging on CD4 may activate the CD95/CD95L-dependent death receptor pathway or, alternatively, activate the Bax-dependent mitochondrial pathway to apoptosis. 34,35 In Jurkat T cells, CD4 engagement by the Leu3a mAb results in a rapid and strong increase of Lck kinase activity, its association with the T-cell 36 This effect can be counteracted by Vav, a signaling molecule that cooperates with CD28 to boost TCR signals.…”

Section: Cell Killing By Soluble Gp120mentioning

confidence: 99%

Mechanisms of apoptosis induction by the HIV-1 envelope

et al. 2005

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The envelope glycoprotein complex (Env) of human immunodeficiency virus-1 (HIV-1) can induce apoptosis by a cornucopia of distinct mechanisms. A soluble Env derivative, gp120, can kill cells through signals that are transmitted by chemokine receptors such as CXCR4. Cell surface-bound Env (gp120/gp41), as present on the plasma membrane of HIV-1-infected cells, can kill uninfected bystander cells expressing CD4 and CXCR4 (or similar chemokine receptors, depending on the Env variant) by at least three different mechanisms.

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“…ϩ T cells (32)(33)(34). Thus, if we want to learn from HIV infection how to suppress the CD4 ϩ T cell function in autoimmune diseases or in transplants or to fight apoptosis in AIDS, we need a detailed understanding of the mechanisms underlying AICD and PCD.…”

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confidence: 99%

Engagement of CD4 Before TCR Triggering Regulates Both Bax- and Fas (CD95)-Mediated Apoptosis

Somma

Tuosto

Montani

et al. 2000

The Journal of Immunology

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In the present study, we have aimed at clarifying the CD4-dependent molecular mechanisms that regulate human memory T cell susceptibility to both Fas (CD95)-dependent and Bcl-2-dependent apoptotic pathways following antigenic challenge. To address this issue, we used an experimental system of viral and alloantigen-specific T cell lines and clones and two ligands of CD4 molecules, Leu-3a mAb and HIV gp120. We demonstrate that CD4 engagement before TCR triggering suppresses the TCR-mediated neosynthesis of the Flice-like inhibitory protein and transforms memory T cells from a CD95-resistant to a CD95-susceptible phenotype. Moreover, evidence that the apoptotic programs were executed while Fas ligand mRNA expression was inhibited led us to analyze Bcl-2-dependent pathways. The data show that the engagement of CD4 separately from TCR influences the expression of the proapoptotic protein Bax independently of the anti-apoptotic protein Bcl-2, whereas Ag activation coordinately modulates both Bax and Bcl-2. The increased expression of Bax and the consequent dissipation of the mitochondrial transmembrane potential (ΔΨm) suggest a novel immunoregulatory function of CD4 and demonstrate that both passive cell death and activation-induced cell death are operative in CD4+ memory T cells. Furthermore, analysis of the mechanisms by which IL-2 and IL-4 cytokines exert their protective function on CD4+ T cells in the presence of soluble CD4 ligands shows that they were able to revert susceptibility to Bax-mediated but not to CD95-dependent apoptotic pathways.

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Induction of CD4⁺ T cell depletion in mice doubly transgenic for HIV gp120 and human CD4

Cited by 25 publications

References 31 publications

HIV-1 Envelope Glycoprotein 120 Increases Intercellular Adhesion Molecule-1 Expression by Human Endothelial Cells

HIV-1 Envelope Glycoprotein 120 Increases Intercellular Adhesion Molecule-1 Expression by Human Endothelial Cells

Mechanisms of apoptosis induction by the HIV-1 envelope

Engagement of CD4 Before TCR Triggering Regulates Both Bax- and Fas (CD95)-Mediated Apoptosis

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Induction of CD4+ T cell depletion in mice doubly transgenic for HIV gp120 and human CD4

Cited by 25 publications

References 31 publications

HIV-1 Envelope Glycoprotein 120 Increases Intercellular Adhesion Molecule-1 Expression by Human Endothelial Cells

HIV-1 Envelope Glycoprotein 120 Increases Intercellular Adhesion Molecule-1 Expression by Human Endothelial Cells

Mechanisms of apoptosis induction by the HIV-1 envelope

Engagement of CD4 Before TCR Triggering Regulates Both Bax- and Fas (CD95)-Mediated Apoptosis

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Induction of CD4⁺ T cell depletion in mice doubly transgenic for HIV gp120 and human CD4