Circulating immune complexes from HIV‐1<sup>+</sup> patients induces apoptosis on‘qc normal lymphocytes

Aceituno, Esther; Castañón, Susana; Jiménez, Concepción; Subirá, D.; Górgolas, Miguel; Fernández-Guerrero, Manuel L.; Ortíz, Fernando; Garcı́a, R.

doi:10.1046/j.1365-2567.1997.00361.x

Cited by 15 publications

(8 citation statements)

References 15 publications

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“…This could be explained by the heterogeneity of the data, which has also been found by other authors 12 . In the present paper we reflect the apoptosis of whole lymphocytes, however, in a previous work from our group 16 , we demonstrated that PHA‐induced apoptosis mediated by circulating immune complexes was directed against CD4 lymphocytes.…”

Section: Discussionsupporting

confidence: 72%

Role of antiretroviral regimes in HIV‐1 patients in reducing immune activation

Jiménez¹,

Molero²,

Jiménez³

et al. 2002

Immunology

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SUMMARYWe assessed whether antiretroviral regimes are able to diminish apoptosis and markers of lymphocyte activation and restore lymphocyte proliferation. T-cell subset, spontaneous and induced apoptosis, CD95 and soluble Fas antigen and cell proliferation were analysed in 41 human immunodeficiency virus type 1-positive patients. Twenty-five were in asymptomatic stage A and 16 were in stage B/C. Thirty-five received antiretroviral treatment: 18 received two inhibitors of reverse transcriptase and one protease inhibitor and 17 received three inhibitors of reverse transcriptase. Six patients did not receive treatment, for different reasons, but continued to participate in the study. Studies were performed at baseline, 3, 6 and 12 months. Levels of CD4 increased slightly until 6 months of antiretroviral treatment, as a whole, in all the patients treated. Naïve CD4 lymphocytes, as well as memory CD4 lymphocytes, remained constant. Spontaneous apoptosis of lymphocytes, after 72 hr of culture, decreased in all patients treated, but to a much smaller extent than phytohaemagglutinin-induced apoptosis. In both groups treated, levels of soluble Fas decreased until 6 months of treatment and then increased again. Lymphocyte proliferation reached normal levels after 1 year of treatment. In patients without treatment CD4 cells decreased slowly and no modification in activation markers was found. Antiretroviral regimes decrease immune activation as well as viral load and this deactivation restores lymphocyte proliferation.

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Section: Discussionsupporting

confidence: 72%

Role of antiretroviral regimes in HIV‐1 patients in reducing immune activation

Jiménez¹,

Molero²,

Jiménez³

et al. 2002

Immunology

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“…Induction of apoptosis in normal lymphocytes by circulating immune complexes from HIV-1 1 patients, acceleration of Fas-mediated activation-induced human lamina propria T cell apoptosis by HIV-1 gp120, and sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120 were reported in the literature. [20][21][22] However, we believe that the main mechanism for elimination of IC-coated CD4 1 and sFas, sFasL, AND CD4 DEPLETION 333 25,26 increased phagocytosis of immunoglobulincoated lymphocytes was observed by Nebe et al, 27 and complement activation by recombinant HIV-1 glycoprotein gp120 was shown by Süsal et al 28,29 The contribution of apoptosis to CD4 1 cell depletion is a controversial subject. Our observations agree with studies of others reporting an upregulation of sFasL in CD4 1 cells of HIV-1-infected individuals, particularly during nonlymphopenic stages of the disease.…”

Section: Discussionmentioning

confidence: 94%

Increased Soluble Fas in HIV-Infected Hemophilia Patients with CD4⁺and CD8⁺Cell Count Increases and Viral Load and Immune Complex Decreases

Daniel

Süsal

Weimer

et al. 2001

AIDS Research and Human Retroviruses

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Previous studies interpreted increases of soluble Fas (sFas) in the plasma during disease progression in HIV-infected patients as evidence of increased apoptosis of CD4(+) lymphocytes. We studied whether sFas and sFas ligand (sFasL) plasma levels are associated with CD4(+) and CD8(+) lymphocyte counts, plasma viral load, and IgM, IgG, C3d, and gp120 complexes on circulating CD4(+) blood lymphocytes in long-term surviving HIV-infected hemophilia patients, most of whom were receiving HAART. Twenty-six hemophilia patients who were infected with HIV in the early 1980s were investigated in 1997, 1998, and 1999. HAART was initiated in 1996 and 1997 in most patients. Lymphocyte subpopulations and immune complex-coated CD4(+) lymphocytes in the blood were investigated by flow cytometry, plasma viral load (HIV-1 mRNA copies/ml plasma) was tested with HIV-1 QT Nuclisens kits, sFas (ng/ml) and sFasL (ng/ml) plasma levels were measured with MBL ELISA kits, and the in vitro response of patient lymphocytes was tested in cell cultures. During the period from 1997 to 1999 we observed an increase in sFas plasma levels (p = 0.003) as well as in CD4(+) (p = 0.004) and CD8(+) (p = 0.023) cell counts; a decrease in IgG (p = 0.047), C3d (p = 0.024), and gp120 (p = 0.001)-coated CD4(+) lymphocytes in the blood; and a decrease in the number of impaired mitogen stimulation assays (p = 0.013). sFas was negatively associated with viral burden (r = -0.662, p = 0.0002) as well as with CD4(+)IgM(+) (r = -0.554, p = 0.004), CD4(+)IgG(+) (r = -0.431, p = 0.031), CD4(+)C3d(+) (r = -0.551, p = 0.041), and CD4(+)gp120(+) (r = -0.430, p = 0.041) blood lymphocytes, CD8(+)DR(+) cell counts (r = -0.700, p = 0.016), and impaired in vitro responses of patient lymphocytes to PHA (r = -0.475, p = 0.016). sFasL was negatively associated with total lymphocyte counts (r = -0.433, p = 0.027), as well as with absolute numbers of CD3(+) (r = -0.492, p = 0.011) and CD8(+) (r = -0.432, p = 0.027) cells. We conclude that, contrary to expectations, sFas plasma levels increased in long-term surviving HIV-infected hemophilia patients receiving HAART, concomitant with increases in CD4(+) and CD8(+) cell counts. Increased sFas may reflect the growing pool of T lymphocytes that recovers because of a decreasing viral burden and a decreasing immune complex load of CD4(+) lymphocytes.

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“…In addition, although the paracrineregulated apoptosis of uninfected cells has been observed in both HIV and ILTV infections (6-8) ( Fig. 5), several molecules from the host cell and HIV that are essential for the apoptosis of uninfected T cells have been identified (12)(13)(14). However, the exact soluble molecules from the host cell or virus that induce this paracrine-regulated mechanism during ILTV infection remain unknown.…”

Section: Discussionmentioning

confidence: 99%

“…More than 60% and 99% of apoptotic CD4 ϩ T cells are uninfected cells during acute and established HIV infection, respectively (8). Many mechanisms, including activation-induced cell death (9,10), changes in mitochondrial permeability (11), gp120/160-induced apoptosis (12), and autologous cell-mediated killing (13,14), have been proposed as possible triggers of HIV-associated apoptosis in uninfected cells. Although the apoptosis of uninfected cells during infection with other viruses is rarely reported, it is possible that the promotive effect of apoptosis on some HSV-associated diseases, such as herpes simplex encephalitis, is also due to the killing of uninfected cells by viral infection.…”

Section: Abstract Alphaherpesviruses Virus-host Interactions Paracrmentioning

confidence: 99%

Gallid Herpesvirus 1 Initiates Apoptosis in Uninfected Cells through Paracrine Repression of p53

Gao

Shao

et al. 2018

J Virol

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Apoptosis is a common innate defense mechanism of host cells against viral infection and is therefore suppressed by many viruses, including herpes simplex virus (HSV), via various strategies. A recent study reported the apoptosis of remote uninfected cells during Gallid herpesvirus 1 (GaHV-1) infection, yet little is known about this previously unknown aspect of herpesvirus-host interactions. The aim of the present study was to investigate the apoptosis of uninfected host cells during GaHV-1 infection. The present study used and models, which avoided potential interference by host antiviral immunity, and demonstrated that this GaHV-1-host interaction is independent of host immune responses and important for both the pathological effect of viral infection and early viral dissemination from the primary infection site to distant tissues. Further, we revealed that GaHV-1 infection triggers this process in a paracrine-regulated manner. Using genome-wide transcriptome analyses in combination with a set of functional studies, we found that this paracrine-regulated effect requires the repression of p53 activity in uninfected cells. In contrast, the activation of p53 not only prevented the apoptosis of remote uninfected cells and subsequent pathological damage induced by GaHV-1 infection but also delayed viral dissemination significantly. Moreover, p53 activation repressed viral replication both and , suggesting that dual cell-intrinsic mechanisms underlie the suppression of GaHV-1 infection by p53 activation. This study uncovers the mechanism underlying the herpesvirus-triggered apoptosis of remote host cells and extends our understanding of both herpesvirus-host interactions and the roles of p53 in viral infection. It is well accepted that herpesviruses suppress the apoptosis of host cells via various strategies to ensure sustained viral replication during infection. However, a recent study reported the apoptosis of remote uninfected cells during GaHV-1 infection. The mechanism and the biological meaning of this unexpected herpesvirus-host interaction are unclear. This study uncovers the mechanisms of herpesvirus-triggered apoptosis in uninfected cells and may also contribute to a mechanistic illustration of paracrine-regulated apoptosis induced by other viruses in uninfected host cells.

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Circulating immune complexes from HIV‐1⁺ patients induces apoptosis on‘qc normal lymphocytes

Cited by 15 publications

References 15 publications

Role of antiretroviral regimes in HIV‐1 patients in reducing immune activation

Role of antiretroviral regimes in HIV‐1 patients in reducing immune activation

Increased Soluble Fas in HIV-Infected Hemophilia Patients with CD4⁺and CD8⁺Cell Count Increases and Viral Load and Immune Complex Decreases

Gallid Herpesvirus 1 Initiates Apoptosis in Uninfected Cells through Paracrine Repression of p53

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Circulating immune complexes from HIV‐1+ patients induces apoptosis on‘qc normal lymphocytes

Cited by 15 publications

References 15 publications

Role of antiretroviral regimes in HIV‐1 patients in reducing immune activation

Role of antiretroviral regimes in HIV‐1 patients in reducing immune activation

Increased Soluble Fas in HIV-Infected Hemophilia Patients with CD4+and CD8+Cell Count Increases and Viral Load and Immune Complex Decreases

Gallid Herpesvirus 1 Initiates Apoptosis in Uninfected Cells through Paracrine Repression of p53

Contact Info

Product

Resources

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Circulating immune complexes from HIV‐1⁺ patients induces apoptosis on‘qc normal lymphocytes

Increased Soluble Fas in HIV-Infected Hemophilia Patients with CD4⁺and CD8⁺Cell Count Increases and Viral Load and Immune Complex Decreases