Immune dysregulation and CD4+ T cell loss in HIV-1 infection

Meyaard, Linde; Miedema, Frank

doi:10.1007/bf00813499

Cited by 13 publications

(2 citation statements)

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“…The progressive loss of CD4 + T-cells during HIV infection follows two patterns: the amount of HIV-infected CD4 + T-cells decreases sharply during acute infection [113,114] and the plasma CD4 + T-cell population is gradually drained further during chronic infection [115,116]. Some HIV-infected T-cells will survive immune clearance and become long-lived resting memory CD4 + cells, which harbor the replication-competent HIV provirus [117,118].…”

Section: The Upregulation Of Immune Checkpoint Proteins Helps To Estamentioning

confidence: 99%

Immune Checkpoints in Viral Infections

Cai

Liu

Zhong

et al. 2020

Viruses

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As evidence has mounted that virus-infected cells, such as cancer cells, negatively regulate the function of T-cells via immune checkpoints, it has become increasingly clear that viral infections similarly exploit immune checkpoints as an immune system escape mechanism. Although immune checkpoint therapy has been successfully used in cancer treatment, numerous studies have suggested that such therapy may also be highly relevant for treating viral infection, especially chronic viral infections. However, it has not yet been applied in this manner. Here, we reviewed recent findings regarding immune checkpoints in viral infections, including COVID-19, and discussed the role of immune checkpoints in different viral infections, as well as the potential for applying immune checkpoint blockades as antiviral therapy.

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Section: The Upregulation Of Immune Checkpoint Proteins Helps To Estamentioning

confidence: 99%

Immune Checkpoints in Viral Infections

Cai

Liu

Zhong

et al. 2020

Viruses

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“…In vivo studies showed a significantly reduced number of IL-2 producing T cell clones in AIDS patients. 78 Since T cells from HIV-1-infected individuals are impaired in their capacity to produce IL-2, necessary for intact T cell proliferative responses, treatment with IL-2 is a logical form of immune therapy. Several studies have been published on IL-2 therapy, all in individuals treated simultaneously with anti-viral drugs to inhibit viral replication.…”

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confidence: 99%

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1999

Leukemia

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Chimpanzee CD4⁺ T cells are relatively insensitive to HIV‐1 envelope‐mediated inhibition of CD154 up‐regulation

et al. 2008

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CD40-CD154 interaction forms a key event in regulation of crosstalk between dendritic cells and CD4 T cells. In human immunodeficiency virus (HIV)-1 infected patients CD154 expression is impaired, and the resulting loss of immune responsiveness by CD4+ T cells contributes to a progressive state of immunodeficiency in humans. Although chimpanzees are susceptible to chronic HIV-1/SIVcpz infection, they are relatively resistant to the onset of AIDS. This relative resistance is characterized by maintenance of CD4 + T cell populations and function, which is highly compromised in human patients. In our cohort of chronically HIV-1-and SIVcpz-infected chimpanzees, we demonstrated the capacity to produce IL-2, following CD3/CD28 stimulation, as well as preserved CD154 up-regulation. Cross-linking of CD4 with mAb was found to inhibit CD3/CD28-induced up-regulation of CD154 equally in chimpanzees and humans. However, specific cross-linking with trimeric recombinant HIV-1 gp140 revealed reduced sensitivity for inhibition of CD154 up-regulation in chimpanzees, requiring fourfold higher concentrations of viral protein. Chimpanzee CD4 + T cells are thus less sensitive to the immune-suppressive effect of low-dose HIV-1 envelope protein than human CD4 + T cells.Key words: Chimpanzee Á CD154 Á Cytokine Á HIV-1 Á Pathogenesis IntroductionHuman immunodeficiency virus type 1 (HIV-1) infection in humans is characterized by a precipitous loss of immune competence, eventually allowing the establishment of opportunistic infections and cancers [1,2]. This loss of immune function is ultimately observed at later stages as a peripheral decrease in the number of CD4 + T cells [3,4]. However, before the numerical loss of CD4 + T cells is apparent, HIV-1-infected individuals already have reduced antigen-specific and mitogen-stimulated CD4 + T cell responses [5][6][7][8][9][10][11][12]. These defects include diminished proliferative capacity and a functional loss in the ability to produce key cytokines. Induction of these important immunomodulatory cytokines is strongly dependent on dendritic cell (DC)-T cell interaction. Exposure to antigen will lead to DC activation [13][14][15], induce migration to lymphoid tissues and result in antigen presentation to T cells via MHC-TCR/CD3 interaction [16]. Subsequent activation of antigen-specific T cells leads to CD154 up-regulation which, via binding to CD40 on the DC, induces DC maturation, which is accompanied by up-regulation of the costimulatory molecules CD80 and CD86 and by IL-12 secretion [21,[27][28][29][30][31][32]. In addition, reduced capacity to produce IL-2 and consequential reduced antigen-specific T cell proliferation were reported [8,26], which can be restored via addition of IL-2 or via CD28 costimulation [5,33]. Cross-linking of CD4 with mAb or with HIV-1 envelope protein results in an inhibition of the CD3-mediated up-regulation of CD154 via an impairment of the normal CD3 signal transduction cascade [34,35]. This perturbation of the normal cell activation and CD154 upregulatory pat...

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Immune dysregulation and CD4+ T cell loss in HIV-1 infection

Cited by 13 publications

References 162 publications

Immune Checkpoints in Viral Infections

Immune Checkpoints in Viral Infections

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Chimpanzee CD4⁺ T cells are relatively insensitive to HIV‐1 envelope‐mediated inhibition of CD154 up‐regulation

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Immune dysregulation and CD4+ T cell loss in HIV-1 infection

Cited by 13 publications

References 162 publications

Immune Checkpoints in Viral Infections

Immune Checkpoints in Viral Infections

True

Chimpanzee CD4+ T cells are relatively insensitive to HIV‐1 envelope‐mediated inhibition of CD154 up‐regulation

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Chimpanzee CD4⁺ T cells are relatively insensitive to HIV‐1 envelope‐mediated inhibition of CD154 up‐regulation