Enhancement of Antigen Driven Lymphocyte Proliferation Secondary to GP41-Induced B7 Expression on Adherent Monocytes

Kolber, Michael A.; Saenz, María O.

doi:10.1006/cimm.2001.1882

Cited by 3 publications

(2 citation statements)

References 25 publications

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“…Although CD86 molecules are constitutively expressed on monocyte surfaces, CD80 expression requires cell activation. Adhesion of monocytes to tissue-culture plates, as performed in this study, has been demonstrated to provide the activation signals needed [41] and to induce functional CD80 expression [42]. In our experiments, freshly isolated human monocytes were devoid of detectable surface CD80 molecules, which were rapidly induced during adhesion.…”

Section: Discussionmentioning

confidence: 55%

Hypoxia reduces CD80 expression on monocytes but enhances their LPS-stimulated TNF-α secretion

Lahat

Rahat

Ballan

et al. 2003

Journal of Leukocyte Biology

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Monocytes/macrophages in ischemic tissues are involved in inflammation and suppression of adaptive immunity via secretion of proinflammatory cytokines and reduced ability to trigger T cells, respectively. We subjected human mononuclear cells and mouse macrophages to hypoxia and reoxygenation, the main constituents of ischemia and reperfusion, and added lipopolysaccharide (LPS) to simulate bacterial translocation, which frequently accompanies ischemia. We monitored the secretion of tumor necrosis factor alpha (TNF-alpha) and the surface expression of human leukocyte antigen-DR and the costimulatory molecules CD80 and CD86 on monocytes/macrophages. Hypoxia selectively reduced the surface expression of CD80 (P<0.01), and synergistically with LPS, it enhanced TNF-alpha secretion (P<0.003). Reoxygenation reversed both phenomena. In the mouse macrophage cell line RAW 264.7, hypoxia reduced the surface expression of CD80 and increased its concentrations in the supernatants (P<0.01). Down-regulation of the mRNA coding for the membrane-anchored CD80 was observed, suggesting that hypoxia triggers alternative splicing to generate soluble CD80. Cumulatively, these results suggest that hypoxia simultaneously affects monocytes/macrophages to enhance inflammation and reduce their ability to initiate adaptive-immunity responses associated with ischemic injury.

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Section: Discussionmentioning

confidence: 55%

Hypoxia reduces CD80 expression on monocytes but enhances their LPS-stimulated TNF-α secretion

Lahat

Rahat

Ballan

et al. 2003

Journal of Leukocyte Biology

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“…In PBMC an indirect effect on T cell activation may occur following the interaction between gp120/160 and other CD4 ϩ cells, such as monocyte/macrophages. In this regard, treatment of monocyte/ macrophages with gp41 (44) or with oligomeric rEnv (27) results in the up-regulation of T cell-activating factors such as the T cell costimulatory molecule, B7 (44), and the cytokine, IL-1␤ (27).…”

Section: Discussionmentioning

confidence: 99%

HIV Envelope Induces Virus Expression from Resting CD4+ T Cells Isolated from HIV-Infected Individuals in the Absence of Markers of Cellular Activation or Apoptosis

Kinter

Umscheid

Arthos

et al. 2003

The Journal of Immunology

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Resting CD4+ T cells containing integrated HIV provirus constitute one of the long-lived cellular reservoirs of HIV in vivo. This cellular reservoir of HIV had been thought to be quiescent with regard to virus replication based on the premise that HIV production in T cells is inexorably linked to cellular activation as determined by classical activation markers. The transition of T cells within this HIV reservoir from a resting state to an activated HIV-producing state is believed to be associated with a shorten life span due to susceptibility to activation-associated apoptosis. Evidence is mounting, however, that HIV production may occur in T cells that have not undergone classic T cell activation. HIV encodes several proteins, including envelope and Nef, which trigger a variety of signaling pathways associated with cellular activation, thereby facilitating HIV replication in nondividing cells. The present study demonstrates that production of infectious virus from resting CD4+ T cells isolated from HIV-infected individuals can be induced following exposure of these cells to HIV-1 recombinant (oligomeric gp140) envelope protein. Envelope-mediated induction of HIV expression occurs in the presence of reverse transcriptase inhibitors and is not associated with markers of classic T cell activation, proliferation, or apoptosis. The ability of HIV envelope to induce virus replication in HIV-infected resting CD4+ T cells without triggering apoptosis provides a mechanism for the virus itself to directly participate in the maintenance of HIV production from this cellular reservoir.

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Antigen-Presenting Cell Modulation Induces a Memory Response to p24 in Peripheral Blood Leukocytes from Human Immunodeficiency Virus-Infected Individuals

Kolber

Saenz

2003

Clin Vaccine Immunol

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The accurate determination of human immunodeficiency virus type 1 (HIV-1)-specific proliferative responses is critically important when evaluating immune recovery after highly active antiretroviral therapy. Using a new assay to enhance proliferative responses to recall and HIV antigen, we addressed the questions of whether viral load affects cellular immunity and whether long-term viral load suppression results in loss of antigen-specific responder cells. This assay is based on the fact that lipopolysaccharide (LPS) can augment proliferative responses to antigen after monocyte adherence to a tissue culture plate. Twenty-six HIV-1-infected individuals donated peripheral blood leukocytes (PBL). Proliferation assays against p24, using LPS and cell adherence, were performed on all samples. Medical record abstraction provided information on CD4 cell nadir and time of viral load suppression. PBL from HIV-1-infected individuals with a viral load of <200 copies/ml had a significant proliferative response and a stimulation index of >5 to p24 (12 of 15) compared to those with a viral burden (2 of 11), using the LPS-adherence assay. Proliferative responses to p24 could be found in PBL from virally suppressed donors independent of the CD4 cell nadirs and in the majority of the donors who were virally suppressed for >10 months (7 of 10). The data presented here demonstrate that LPS and monocyte adherence provide a sensitive and specific way to boost proliferative responses to recall and HIV antigens.The impact of highly active antiretroviral therapy (HAART) on immune reconstitution has been clearly demonstrated in those individuals with advanced disease. When a human immunodeficiency virus type 1 (HIV-1)-infected individual with AIDS is aggressively treated with antiretroviral therapy, the viral load is suppressed and the CD4 count frequently is elevated above 200 cells/mm 3 . This permits discontinuation of prophylaxis for opportunistic infections and, in the long term, results in an enhanced period of survival and a decrease in disease progression. However, there are still numerous questions regarding the level of cellular immunity and which factors affect this parameter.Although it is known that defects in the immune repertoire exist early in infection (31, 36) and progress as the disease advances (12), the ability to reconstitute immunity most likely depends on numerous host factors and comorbid conditions. As a further confounding variable, the role of the viral load as an independent predictor of disease progression for CD4 counts greater than 350 cells/mm 3 has been difficult to ascertain (22), even in light of the in vitro data suggesting immunesuppressive effects of the virus on proliferation to recall and HIV-1 antigens (28,30,37). Incomplete reconstitution in some individuals is suggested by the fact that the incidence of malignancy continues to be high in individuals infected with and treated for their HIV-1 disease (9,27).With the ongoing efforts in HIV vaccine research, the ability to identify individuals with ...

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Enhancement of Antigen Driven Lymphocyte Proliferation Secondary to GP41-Induced B7 Expression on Adherent Monocytes

Cited by 3 publications

References 25 publications

Hypoxia reduces CD80 expression on monocytes but enhances their LPS-stimulated TNF-α secretion

Hypoxia reduces CD80 expression on monocytes but enhances their LPS-stimulated TNF-α secretion

HIV Envelope Induces Virus Expression from Resting CD4+ T Cells Isolated from HIV-Infected Individuals in the Absence of Markers of Cellular Activation or Apoptosis

Antigen-Presenting Cell Modulation Induces a Memory Response to p24 in Peripheral Blood Leukocytes from Human Immunodeficiency Virus-Infected Individuals

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